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 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.
Pierce tries to crack a coded message left in a newspaper by someone who may be connected to a murder. But time isn’t on his side as another victim’s life could be in danger.
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 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.
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 is tipped off by a former student about a potential conspiracy to cover up the murder of a U.S. Senator. But the situation soon spirals into a nightmare in which the people Daniel should be able to trust might instead be working against him.
Moretti learns there may be some truth to Pierce’s conspiracy theory when new evidence shows up online. Meanwhile, Pierce's new doctor forces him to face the truth about Natalie.
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 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.
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.
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 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.
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.
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.
Pierce investigates a gruesome stabbing at a psychiatric hospital. Guided by his hallucination of Sigmund Freud, Pierce becomes convinced the hospital is full of dark secrets.
Donnie tries to help a war hero suffering from a neurological disorder, but what starts out as a good deed ends up having major implications. Meanwhile, Pierce gets an unexpected surprise when a fling from his past shows up.
Morretti faces criminal charges after taking things into her own hands while working on a dangerous case. Pierce and Donnie strive to clear her name, but as conflicting evidence builds, even Kate begins to question her own innocence
Dean has to turn on the charm to win a place at CLMU. Pierce fights a case for an autistic teen who's suspected of murder with the help of a hallucination from hall of famer Mordecai "Three Finger" Brown.
Pierce and Lewicki are caught off guard when Lewicki's brother Kenny shows up unannounced. In an unwelcome turn of events, Kenny is named the key suspect in a homicide case, leaving Pierce torn between helping a friend and serving justice. Meanwhile, Lewicki is approached with a tantalizing offer that makes him question Pierce's loyalty to him.
Tensions arise between the CIA and FBI after Pierce receives a tip that the CIA might be assassinating U.S. citizens. Things become more complicated when one of Pierce's close friends is murdered. Meanwhile, Moretti tries to overcome her trust issues with Donnie.
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.
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 Dekan 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.
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 (guest star Peter Coyote) pays him a visit.
Moretti calls on Pierce to examine Elena Douglas (guest star Rya Kihlstedt), 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.
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 (guest star Peter Coyote) 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. Featuring guest star Jeff Branson.
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. Featuring guest star Francesca Eastwood.
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 (guest star Robert Curtis Brown), who believes it will only exacerbate Pierce's condition.
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 (guest star Brooke Nevin) courts Donnie to run for political office.
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 (guest star Peter Coyote) after he assaults someone at the assisted living facility.