Best friends Lizzie and Sam share a drink at their neighborhood dive bar. Sam is nervous: it's her third date with nice guy, Brad. And everyone knows about the the third date -- the sex date. Lizzie scolds her for not having had sex already, which is a violation of the rules passed down to them by their recently married friend, Sienna. Sam acts on Lizzie's advice and seduces Brad, only to have him dump her immediately after their encounter when his girlfriend texts him that she wants him back. Lizzie insists that Sam "get underneath another man" right away, and the two friends go prowling at an upscale club. Lizzie focuses on getting someone to buy them top-shelf drinks, while Sam makes the acquaintance of Jason, who turns out to be Lizzie's new co-worker. Lizzie breaks it up, saying that Jason is too clingy and moves on to her own quest -- the sexy, casually dressed guy sitting at the bar, reading a book. Lizzie's initial encounter with this man she dubs "Dirty Hot Guy" begins hot and flirty but ends in mutual insults. And when -- adding insult to injury -- her ex, Drew, comes in with another girl, Lizzie is determined not to let it get to her. She and Sam cruise a jiu-jitsu studio, but get little more than hot and sweaty. Afterwards, Lizzie encounters the Dirty Hot Guy in the dive bar and takes him home for sex. Sam learns that her current major crush, Richard, will be at the R Bar; she and Lizzie make a beeline for the place, hoping for a "chance" encounter.

Sam starts stalking Richard and waits outside his apartment house so she can bump into him when he comes home. He's with his neighbor, Morgan, so Sam declines his offer to come inside. Lizzie scolds Sam for not accepting the invitation and outlasting Morgan, a violation of the "last woman standing" rule. Sam follows Richard on twitter and crashes a fantasy football party to be near him but Richard ends up leaving the party while Sam is in the bathroom. Meanwhile, Lizzie and Jason handle a sexual harassment case for Kyra, who was fired from a cupcake store when she refused sexual advances from her supervisor. Lizzie goes undercover, but can't get supervisor, Jessie, to come on to her, no matter how she flirts. Finally, she corners him in the back room and seduces him. She tells Kyra that she couldn't get the goods on her tormentor, only to learn that Kyra was harassed by Johnnie, the boss's son. Lizzie goes back to the cupcake store to get evidence against Johnnie, leaving Sam at the dive bar with Richard and Morgan. Sam out-drinks Morgan, who passes out; she takes Richard home with her, but he is too drunk to get it up and just falls asleep.

Richard cancels a date with Sam, who complains to Lizzie that she's tired of the game men and women play with one another. Lizzie suggests they find a place where the guys don't know the rules, and settles on a Mexican place on college night. The girls pick up Stevie and Len, business/finance majors, and go back to their place. Lizzie and Len have sex, but Stevie is so excited he comes before Sam can even get him undressed. In the morning, the girls discover that Len and Stevie are both just barely legal and living at home -- they graduated from the "University" prep school. Meanwhile, Jason is romancing Nicole, a marine botanist who picked him up with a candid line at the farmers' market. Thanks to Lizzie, he has some doubts about her sincerity, but Nicole's directness wins him over. He goes out with her and they end the night with an energetic sexual workout. In the morning, Nicole leaves, promising to call Jason. A few days later, he bumps into Lizzie and Sam at the farmers' market. They see Nicole using the same "candid" line on another guy, and Jason realizes that Lizzie was right -- fake sincerity is Nicole's game. Jason and the girls adjourn to a nearby joint to drown their sorrows.

Richard cancels a date with Sam, who complains to Lizzie that she's tired of the game men and women play with one another. Lizzie suggests they find a place where the guys don't know the rules, and settles on a Mexican place on college night. The girls pick up Stevie and Len, business/finance majors, and go back to their place. Lizzie and Len have sex, but Stevie is so excited he comes before Sam can even get him undressed. In the morning, the girls discover that Len and Stevie are both just barely legal and living at home -- they graduated from the "University" prep school. Meanwhile, Jason is romancing Nicole, a marine botanist who picked him up with a candid line at the farmers' market. Thanks to Lizzie, he has some doubts about her sincerity, but Nicole's directness wins him over. He goes out with her and they end the night with an energetic sexual workout. In the morning, Nicole leaves, promising to call Jason. A few days later, he bumps into Lizzie and Sam at the farmers' market. They see Nicole using the same "candid" line on another guy, and Jason realizes that Lizzie was right -- fake sincerity is Nicole's game. Jason and the girls adjourn to a nearby joint to drown their sorrows.

Lizzie and Sam are at the dive bar when the bitchy Mariposa sidles up beside them and intimidates Jason into buying her a drink. Afterwards, Lizzie and Sam overhear Mariposa on the phone and realize that Latin spitfire is just an assumed persona for Mildred, an ordinary girl who has learned how to channel her inner b**ch to get what she wants. The three women chat over coffee. Lizzie and Mariposa are both attracted to the same cute Waiter, and a challenge goes out – let the biggest b**ch win. Sam channels her inner b**ch with bike messenger Ryan and gets him to go home with her. They have wild, primal sex, but his interest fades in the morning when Sam inadvertently reverts to her nice girl self. Lizzie and Mariposa compete for the Waiter, but Lizzie can’t beat the master and Mariposa waltzes away with the prize. Later, a the dive bar, a Voluptuous Woman b**chily refuses to say where she bought her dress, so Lizzie cuts the label out of her garment. The dress is from a plus size shop - the Woman was embarrassed about shopping there. Lizzie feels guilty about her brazen behavior and apologizes. Sam goes home, and a deflated Lizzie stays at the dive bar. The Dirty Hot Guy sits down next to her, offers companionable silence, and buys her a drink.

Lizzie and Sam see a plain woman with a handsome younger man and wonder how she holds his attention. Someone suggests she has a "magic p**sy," something no one can define. Lizzie is determined to unravel the mystery. First, she and Sam attend a tantric yoga class, but are tossed out when they start laughing. The girls are talking things over when Cheyenne, Tyler's sub at the bar, volunteers that she once had a magic p**sy -- until she had a baby. Next, the girls try a special steam treatment for their nether regions at a Korean spa, but are horrified when they learn it's a fertility treatment. Two days later, they still don't have an answer to their question. Tyler, who is gay, suggests that maybe it's really a magic mouth, and tells them about the most popular girl in his year at the University of Illinois. The Dirty Hot Guy comes in and Lizzie ambles over to talk to him. He tells her he knows the secret to a magic p**sy -- it's confidence. Just then, his date arrives -- an older woman who exudes confidence and is not threatened to see him with Lizzie. Later, Lizzie tells Sam that she misses Drew, her ex, and wonders if he's happy with his pretty younger girlfriend.

Sam and Danny have daytime sex, which alarms Lizzie -- Sam's falling for her f**k buddy, a violation of one of the top ten rules. Kaylie dates her new f**k buddy and doesn't find it a problem; Sam wonders if she can pull off the same trick. Her co-worker, Kate, thinks casual sex is folly and tells Sam so, but when her boyfriend dumps Kate, Sam sees the wisdom of remaining uninvolved. Despite her good intentions, Sam accepts Danny's impromptu invitation to the movies and afterwards, to grab a bite to eat. She invites him back to her place, but he declines. Lizzie tells her she had it coming for breaking the rules. Then Danny calls and invites Sam for drinks. He tells her that he has to keep his dating life and his sex life separate, and breaks up with her. Sam drowns her sorrows in a pint of ice cream. The sounds of Kaylie and Jordan having energetic role-playing sex as "Trinity" and "Neo" drives her from her apartment and into the dive bar. Lizzie tells her that horniness is the price she must pay for breaking the f**k buddy rule. Lizzie and Tyler get so hot thinking about Trinity and Neo that they rush out to a fetish joint, leaving Sam alone yet again.

Kaylie is with Lizzie and Sam at the dive bar, where they see a guy who looks like Jordan pick up a busty Blonde. Kaylie is devastated. Lizzie and Sam tell her that all men cheat, and offer examples from their pasts. They urge her to even the score by making him jealous. Lizzie and Sam stalk Jordan, trying to catch him cheating. They follow him to the gym and to breakfast; that night, they watch as someone who looks like him enters his apartment building with the Blonde in tow. Sam uses a ruse to get them into Brad's apartment so they can spy from across the alley. Sam stays behind, has sex with Brad, and dumps him like he did her. Lizzie and Sam present their inconclusive evidence to Kaylie, and tell her it's time to make Jordan cry. Kaylie has Tyrone escort her to the dive bar. Jordan walks in, sees them together, and is heartbroken. When presented with the "evidence," he tells them that he moved that weekend and spent it unpacking -- he isn't the guy on the video. Kaylie and Jordan make up and leave together; Tyrone joins the busty Blonde; Jason tells Lizzie and Sam that their rules don't work, which is why they are alone. Sam goes home and listens to Kaylie and Jordan having sex on the other side of the wall.

Lizzie and Sam visit a gay bar with Tyler, and argue about Sam's penchant for unavailable men. Lizzie flirts with gay boy Mark and gets drunk; he takes her home and has sex with her. Lizzie tells Sam of the encounter and the two friends ponder how to tell if a guy is straight or gay. Sam is curious about Devon, a cute new co-worker, but picks up mixed clues to his orientation from his conversation, computer search history, and behavior. They host a launch party at a tattoo parlor for b**chy client, Fiona's, photo book. Sam invites Tyler to see if he can get a read on Devon, but even Tyler is stymied. Tyler is delighted with the b**chy Fiona, though, and surprises Lizzie and Sam by having sex with her in a back room. At the party's end, Sam flat-out asks Devon if he's straight or gay. He suggests she check his relationship status, which leaves the matter unsettled: Devon is involved with "Chris." Lizzie finally gets an answer to her questions about Mark when she discovers that he is actually straight, and masquerades as gay to get women. Sam resigns herself to never being sure about Devon. Both women are confused by Tyler, who says that despite having had sex with Fiona, he's absolutely sure he's one hundred percent gay.

Lizzie and Sam get a surprise visit from Sienna. Operating on the premise that men can't resist a woman who is "taken," they masquerade as Lizzie's bachelorette party and go on the prowl. Lizzie lets Marco pick her up, and takes him back to her place for one last fling. Sienna learns of Sam's interest in Richard and Jason, and insists that they attack the easier target -- Jason. They hack into his e-mail to find out where he will be, then follow him and his date, Lulu, to a movie theatre. When the film ends, Sienna creates a distraction, but Sam is unable to pry Jason away from Lulu. She and Sienna follow them to Jason's apartment building and spy through the window as they have sex. Lizzie tells Marco she's not engaged; he tells her he's married. Sienna says farewell to her friends and returns to the suburbs. Sam thinks her marriage is in trouble due to all her silly rules. She decides to get out of Jason's way and arranges to bump into Lulu to tell her what good man she's found. Sam feels pretty good about doing the right thing, but Lulu is appalled at the thought of dating a nice guy, and ditches Jason.

Sam is angry and distracted, so Lizzie sends her to see Dr. Feelgood. The doctor prescribes something for anxiety and depression, which Sam resents -- she just needs something to help her focus. Lizzie puts her in touch with Pill Pusher Patty, who trades some uppers for Sam's scrip. Sam takes the pills and turns into a model of efficiency. When she runs out of pills, she has Patty meet her at a house party she and Lizzie will be attending. Lizzie's ex, Drew, is at the party, as is Richard. When the girls arrive, Sam ignores Richard and makes a beeline for Patty; once she has her pills, Sam finds Richard, who is quite drunk, and takes him home with her. Lizzie finds Drew, who feels down because his new girlfriend is cheating. Lizzie gloats over this development, which only depresses Drew. He withdraws to a bedroom, which is where Patty finds him and consoles him with sex. Lizzie stumbles on them and realizes she's the only one at the party who didn't hook up. Back at her apartment, Sam manages to get Richard into bed. He passes out, penis erect, thanks to another of Patty's pills.

It's just another boring Sunday until Sienna breezes into the dive bar and announces she's staying until her husband apologizes for reading in the bathroom. She decides to show her protégés how to get a man's attention and gets aggressive with a Muscle-Bound Dude sitting at the bar. He's a cop, and he arrests her. Sam is sobered by the incident and thinks that Sienna's rules are guaranteed to keep them alone. She's ready for a change and asks co-worker Kate about her new boyfriend, Shermann. He's a public defender, and agrees to pull a few strings to try to get Sienna released. Sienna's husband, Nathaniel, visits her in jail. She apologizes, he forgives her, and she vows to try to stop sabotaging their relationship. Kate tells Shermann about her 10-date rule, and he suggests they have all 10 dates in one day; at day's end, they can then have sex within her rule. Sam types up all of Sienna's rules and shows Lizzie the ones she questions. Lizzie is reluctant to give up any of them. Sienna is released and bumps into the Muscle-Bound Dude at the desk. He talked to Nathaniel and has agreed to drop the charges. Nathaniel awaits Sienna in the jail's visiting room, where they have sex.

Lizzie and Sam fight over Lizzie's acceptance of Drew's invitation to have drinks. Sam insists that this will lead to another reconciliation and break-up, and that it's time for Lizzie to end the relationship completely. It turns out that this time Drew just wants Lizzie to have her friend at the DMV fix some parking tickets for him -- he has reconciled with his cheating girlfriend. Sam bumps into Jason and lets it slip that she has a crush on him. Jason is free, since Lulu dumped him, and asks Sam out. As Sam readies for her date, Lizzie phones her to meet her at Drew's place, where they watch as a cop boots Drew's car -- Lizzie's revenge and a farewell to Drew. The girls celebrate at the dive bar, toasting their new rules: no more coercing guys to buy them drinks, no more young guys, no more b**ching, no more unrealized sexpectations, no more married guys, drinking contests or ex-boyfriends. Lizzie sees the Dirty Hot Guy and finally introduces herself; his name is Leo. Then Sam gets a text from Richard. She is torn, but opts for Jason. Lizzie and Leo also hook up for the night. Lizzie and Leo spoon contentedly after some hot sex, but sleeping in Jason's arms panics Sam, who gets up and leaves his place. She texts Lizzie to meet her -- she thinks she has just made a huge mistake...