Sydney teams up with Renée - a fugitive on the CIA's most wanted list -- to track down the murderer of a close friend before the killer can strike again. Meanwhile, Jack enlists a reluctant new agent, Thomas Grace (Balthazar Getty), and Weiss struggles to decide whether or not to accept a promotion that would force him to leave his colleagues.

Sydney and Tom discover that Renie has stolen the cryo container, and soon find themselves under siege by a group of mercanaries who want the contents of the container. Meanwhile, Sloane takes matters into his own hands to get himself back into APO.

While the FBI detains and questions Sydney about her past and possible ties to a mysterious Rambaldi doomsday prophecy, Vaughn and Jack must race to free her and find a way to clear her name before her cover is blown and SD-6 is made aware of the situation. Once the rescue op has been launched, in her quest to prove her innocence, Sydney shocks even her usually unflappable father when she makes a chilling discovery that may unravel the mystery of the 500-year-old prophecy – she finds proof that Rambaldi's writings may hold more truth about an alleged weapon of mass destruction - and the fate of her own family.

A Rambaldi artifact prophesizes that an apocalyptic event will soon take place, and Dixon's grief leads Vaughn and agency psychologist Dr. Barnett to question his intentions, as his thirst for revenge on Sloane intensifies. Meanwhile Sloane receives a life-changing revelation from a mysterious monk in Nepal, Sydney and Dixon hunt for the killer who stole the heart from his victim.

Sydney's search for her past leads to a jailed Sark, but their Q&A is cut short when he becomes the ransom for a pair of abducted CIA scientists, whose kidnappers may be tied to the murder of his father. Jack contacts an old friend of sorts for info on Sloane's new world-peace project, and Vaughn makes a decision about his future as an operative.

Sydney and Vaughn are reunited again as a team to prevent Sark from destroying the nation's satellite communications system. Meanwhile, Jack must find a way to stop Marshall from uncovering the identity of a familiar murderer. Sydney accompanies Vaughn and Lauren as they meet with Sloane to ask for a favor.

After being infected with a hallucinogen, Sydney starts to lose touch with reality. Vaughn and Jack must rush to find an antidote before Sydney puts her life - and others next to her - into danger.

Nadia puts her own life - as well Sydney's and Weiss's - in danger after failing to unveil her past through a dangerous criminal. Meanwhile, Vaughn finds a person who is somehow connected to his father and Nadia as well.

Marshall reports to Jack that a microchip, found in Renée Rienne's body, is etched with the name 'Andre Micheaux'. Peyton tells Sloane that Sydney is being sent to Nepal to meet with someone regarding the chip. Sloane sends Anna, now Sydney's doppelgänger, to intercept. When Marshall discovers that the APO office is bugged, Jack frantically tries to reach Sydney to warn her before it is too late.

Sydney and Dixon are sent to Las Vegas to gather information from a K-Directorate agent who has ties to the group that attacked and nearly destroyed SD-6. Meanwhile, Sydney learns some shocking news about Francie's fiancé, Charlie, Will begins his journey in discovering what SD-6 really is, and Jack continues to try to be more of a father to Sydney when he helps her decide whether or not to continue with graduate school.

While on a case to track the activities of Khasinau, a.k.a. "The Man," Sydney runs into her ex-lover, Noah Hicks, who broke her heart and left without saying goodbye five years earlier. Meanwhile, Sydney tells Sloane that she wants to find her mother; Jack is ordered to see CIA psychiatrist Dr. Barnett to help him deal with his churning emotions after discovering that his wife may still be alive; and Will and Francie become suspicious of Sydney's activities after finding one of her airline ticket stubs.

Sydney must decide whether her mother's goodwill gesture was sincere or an attempt to kill her. Will witnesses Francie discussing her restaurant plans with a man whose affiliations are questionable, and Sloane is made a full partner in the malevolent Alliance of Twelve.

Sydney's dealings with her mother lead Jack to take drastic measures to ensure his daughter's safety. Meanwhile Will is confronted by a mysterious woman about resurrecting his story on SD-6.

While Vaughn's life hangs in the balance, Lauren butts heads with Sydney after learning the part she played in his stabbing. Meanwhile, Sydney further questions Sloane's allegiances after he is kidnapped by Kazari Bomani, a kingpin in The Covenant; Jack's cover is jeopardized when he meets with Simon to dig up information on Sydney's missing two years; and Marshall is sent on his second mission with Sydney, posing as a high-stakes, southern gambler.

Sydney's emotions are turned inside-out when she comes face-to-face with Allison, Francie's doppelgänger, who was presumed dead but is now a key figure in The Covenant. Meanwhile Lauren's search for Lazarey's murderer leads her closer to discovering a connection to Sydney, and Sydney begrudgingly is assigned as Sloane's CIA handler.

Sydney and APO attempt to discover whom Gordon Dean is working for and what their end game is. Meanwhile, when the group claiming to have a cure for daughter Nadia continues to play mind games with him, Sloane struggles for control.

Sydney now posing as Anna, brings Peyton a microchip with a device hidden in it. Meanwhile Sloane finishes translating page 47 and reports that only the chosen one can complete the circle, which leads Sark and Sydney on a dangerous mission to a prison. Rachel finally discovers Tom's secret about what happened to his wife.

Sydney and Dixon go on a dangerous case involving the safety of the United Commerce Organization. Francie confronts Charlie about his secret date with another woman, and Will continues to get closer to the truth about Danny's murder.

Sydney must outwit Sark in order to find a crucial piece of intel. Meanwhile, Jack faces Sydney's mother for the first time in almost 20 years. Will finally meets Vaughn and Sloane is haunted by his wife's death.

Sydney's trust in her father begins to fade. Meanwhile, Sydney and Vaughn may have been exposed to a deadly virus while in Taipei; Sloane haunted by Emily's death begins to unravel. Vaughn enlists Will to help research a case.

Sydney must make a life-defining decision regarding her future with the agency, while Sloane re-emerges and continues his obsessive quest to piece together the mysterious Rambaldi artifacts - with the reluctant aid of a kidnapped scientist. Meanwhile, Dixon's marriage is put to the test after he tells his wife the truth about his occupation.

A mysterious Rambaldi device's powers are finally revealed and Sloane has its secrets. Meanwhile, Vaughn begs Dixon to aid the CIA in rescuing Sydney, Will is called upon to participate in a crucial CIA briefing session, and Sydney senses that Francie is keeping secrets.

Sydney discovers a link to her missing two years in the form of Simon Walker, the dangerous and sexy leader of a group determined on retrieving deadly biological weapons. Meanwhile, Vaughn struggles with his own feelings of jealousy and longing while Sydney is on her mission, aware of the pressures his job is putting on his marriage to Lauren. Jack takes matters into his own hands to protect his daughter, purposefully revealing Sydney's deadly secret to Dixon in order to preserve her position inside the CIA.

Sydney and Vaughn are sent to retrieve the Doleac Agenda to gain an advantage over The Covenant. For this, Sydney and Weiss must convince rogue security systems designer Toni Cummings to help the CIA break into a Lethal Response System. Meanwhile, Sark approaches an unlikely ally to kill the Covenant's Cell leaders.

While trying to retrieve a bomb, Sydney and Vaughn are ambushed by unidentified assailants. Meanwhile, Lauren and Sark continue to solidify their new partnership, Sloane divulges a dark secret to Dr. Barnett and Marshall shows the strains of new fatherhood.