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.

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

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.

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

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.

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.