When Donnie finds himself in a compromising situation, he calls Pierce for help. As the evidence begins to stack against Donnie, Pierce and Moretti struggle with their own fears and doubts, as they work to solve the case. During the chaos, Pierce must deal with his father after he assaults someone at the assisted living facility.

After a missing FBI agent turns up dead, Pierce is forced to face the one case he was never able to solve. When they discover that the killer is still out there, Pierce agrees to help Moretti, against the wishes of his therapist, Dr. Rosenthal, who believes it will only exacerbate Pierce’s condition.

When a series of bizarre public murders occur, Pierce realizes that the killer is trying to send a message about inattentional blindness, but Donnie doubts this theory. But Pierce has a trick up his sleeve that can prove his point, and they must scramble to piece together the clues before the clever killer can make any more examples out of innocent victims.

Moretti faces criminal charges after taking matters into her own hands on a dangerous case; Pierce and Donnie try to clear Kate's name.

Pierce's mental stability is questioned and his job threatened when he is accused of stalking his ex-girlfriend, Caroline Newsome. As the situation escalates, Moretti works to find the real stalker with help from a visiting inspector from Canada.

A student tips off Pierce about a potential conspiracy to cover up the murder of a U.S. Senator.

Moretti learns that there may be some truth to Pierce's conspiracy theory; Pierce's new doctor forces him to face the truth about Natalie.

After Dr. Daniel Pierce suffers a traumatic injury, his father and his friend must decide if they should allow him to undergo a high-risk surgery; Pierce begins to question everything he sees and hears.

When a student is found murdered, Pierce tries to find the killer while defending the victim's boyfriend; Pierce must confront his feelings as Kate and Donnie prepare for their wedding day.

After Pierce witnesses a gallery owner die during a seizure caused by a video installation, he convinces Moretti that it was actually a murder. Their search for the killer puts them in the middle of a brazen art heist. As Pierce works on the case, he is forced to re-examine his relationship with Natalie.

When Moretti goes missing the day of her wedding, Pierce and Donnie set off in pursuit of the runaway bride. They soon learn that Kate has been abducted by a dangerous person from Pierce's own past. Now, Pierce and Donnie must risk everything to save Moretti before it's too late.

FBI Agent Kate Moretti asks Dr. Daniel Pierce to determine the mental competency of a man being retried for murder. But the trial takes a shocking and unexpected turn when Pierce’s findings question whether the person standing trial is the same person he was six years ago. Meanwhile, Moretti is unpleasantly surprised to discover that the Assistant U.S. Attorney prosecuting the case is her soon-to-be-ex-husband Donnie Ryan.

Pierce accepts an invitation to work on a case from a renowned environmental activist concerning a chain of abnormal neurological reactions in a group of young girls. However, upon examining the girls, Pierce discovers that a dark secret is at the root of their ailments. Meanwhile, Moretti questions Pierce’s motives in working on a case without her.

Pierce investigates a stabbing at a psychiatric hospital and becomes convinced that the hospital is full of dark secrets.

Donnie tries to help a war hero who suffers from a neurological disorder; Pierce is surprised by an old flame.

Pierce fights for an autistic teen who is under interrogation for murder; Dean Haley attempts to convince a neuroscience prodigy to attend CLMU.

Dr. Daniel Pierce’s picture-perfect new life in Paris is suddenly turned upside down after he is approached by the FBI legat to help with a dangerous international case. Meanwhile, his assistant Max Lewicki and Dean Paul Haley plot to get Pierce to return to Chicago.

When a prosecutor mysteriously drops dead in the middle of a courtroom, Pierce and Moretti go on the hunt for a killer. Meanwhile, Moretti and Donnie make some decisions about their future.

Pierce and Morretti plunge into virtual reality to solve the murder of Kurt Simpson, a man who spent most of his time in a massive multiplayer online game called Caleidoscope. After creating an avatar of himself to investigate the crime, Pierce struggles more than ever to distinguish between reality and fantasy.

When renowned neuroscientist Landon Jennings is found dead, Moretti and Pierce must figure out how someone could have gained access to his impenetrable study in order to kill him. Lewicki finds himself with twice the work when Pierce’s father James moves in with them.

When an infant is reported stolen, Moretti hunts down the kidnapper and makes a very bizarre discovery. As Pierce and Moretti investigate a related murder, they find that there might be another child out there who needs their help. Meanwhile, Donnie and Moretti discuss their future together when Donnie looks into buying a house in the suburbs.

Donnie and Moretti are caught in the crossfire when a sniper shoots up the lobby of the Federal Building. When Pierce determines that the shooter is afraid of Extreme Low Frequency radio waves, he and Moretti take a trip to the Quiet Zone in Virginia, where they think the shooter is hiding out. Meanwhile, an alluring woman named Shelby Buchanan courts Donnie to run for political office.

Pierce and Moretti uncover an international scandal while investigating the murders of a Bangladeshi diplomat and a Chicago reporter; Moretti struggles with the preparations for her upcoming wedding.

Pierce and Moretti take on an extraterrestrial case when a woman reports that aliens have abducted her husband. When Pierce and Moretti arrive to investigate, however, they make a startling discovery. Meanwhile, things heat up between Pierce and his real-life girlfriend, Caroline, but his relationship could be jeopardized if he can't get his imaginary girlfriend, Natalie, out of his mind.

A new brain device to control tremors seems to have a defect that turns out to be far more serious than a technical malfunction, and Pierce partners with Donnie to investigate. Their unlikely alliance is tested when the case escalates to murder. Meanwhile, Lewicki learns a valuable lesson about dating.