When Moretti receives a deathbed confession about the hit-and-run murder of a teenager from 1992, she calls on Pierce to determine the ailing man's credibility. The case becomes complicated, however, when the alleged killer's physician, Dr. Hutchins, reveals that his patient’s tumor has mysteriously disappeared. Pierce and Moretti must dig deeper into the past to uncover the truth behind a shocking series of apparent homicides.

Neuroscience professor Daniel Pierce (Eric McCormack) is recruited by a former student, FBI Agent Kate Moretti (Rachael Leigh Cook), to help out on a case involving the death of a pharmaceutical executive. But Daniel's schizophrenic hallucinations could potentially derail the investigation.

Pierce is enlisted to help crack the case of a murdered mail-order bride. A twist marks the investigation when it's discovered the prime suspect suffers from an unusual condition. Elsewhere, Moretti is drawn to a handsome new professor.

Pierce is called upon to help the FBI investigate the murder of a therapist. Moretti spends more time with Professor Hathaway. And Dean Haley uses Pierce as bait to get a wealthy alumni’s widow to fund a new building.

Lewicki's brother shows up unannounced; Kenny is named the key suspect in a homicide case; Lewicki is approached with an offer that makes him question Pierce's loyalty.

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.

Pierce receives a tip that the CIA might be assassinating U.S. citizens; one of Pierce's close friends is murdered; Moretti tries to overcome her trust issues.

After a young victim with a developmental disorder is taken hostage in a bank robbery, Moretti brings in Pierce to interview the boy. When they finally track down the culprits, they discover the case is about much more than money. Meanwhile, Pierce’s estranged father James pays him a visit.

Moretti calls on Pierce to examine Elena Douglas, a woman who has confessed to murder and claims to be possessed by the Devil. Meanwhile, Donnie and Moretti’s wedding plans hit a bump in the road.

Agent Kate Moretti goes under cover to investigate an animal rights group suspected of foul play; Pierce considers making a confession to Kate.

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.

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 race to find clues when a serial killer from 1986 begins killing again. They catch a break when they learn that one of the victims is actually alive. Moretti's dad, one of the investigators on the original case, offers his daughter advice. Pamela Reed also guest-stars as the mother of the surviving victim, while Armin Shimerman is the victim's psychologist.

When a young man in a cult claims to be hearing the word of God, Pierce must determine if it’s actually the word of God or a life-threatening neurological condition. Pierce and Moretti must also figure out if his murder is linked to his drug past or his new life with an organization that may be scamming people out of their life savings. Roger Bart guest-stars as Ethan Kendrick, a high-powered IRS agent looking into the finances of the organization. Meanwhile, the university gives Pierce an award for his research.

Pierce must take a deep look into his own life when he is brought into a case involving a schizophrenic. Meanwhile, Moretti stops at nothing to impress her new boss at the FBI. Guest star Tom Sizemore plays a top-level Irish mobster, while guest star Edward Furlong plays a would-be tough guy who may have played a crucial role in the crime.

Moretti and Pierce are called upon to solve a crime in their own backyard when a college student is killed in her dorm room. Pierce is forced into the uncomfortable situation of interacting on a personal level with more than one of his students, which forces him to confront difficult truths about his own past. The case comes just as Moretti is beginning to re-evaluate her relationship with Dr. Hathaway.

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.