A retired FBI profiler living a quiet life in the Florida Keys who possesses a tormented gift for empathy that allows him to reconstruct crimes in his mind. He is reluctantly pulled back into duty by his former mentor to hunt down a new serial killer, despite the past trauma caused by Hannibal Lecter.

A physically powerful and deeply disturbed man working at a film processing lab who is driven by a split personality he calls the "Great Red Dragon." Known to the police as "The Tooth Fairy," he commits ritualistic murders of families to fuel his "becoming" into a higher being.

The special agent in charge of the FBI's Behavioral Science Unit and Will Graham's former boss. He is a pragmatic and manipulative leader who is desperate to stop the murders before the next full moon, willing to exploit Graham's fragile psyche to achieve results.

A brilliant forensic psychiatrist and cannibalistic serial killer currently incarcerated in the Chesapeake State Hospital for the Criminally Insane. He serves as a twisted consultant to Graham, simultaneously helping and manipulating the investigation from behind bars.

Will Graham's supportive wife who provides a stabilizing, normal family life for him and her son in Florida. She is deeply protective of Will and hesitant about his return to the FBI, fearing the psychological toll the investigation will take on their family.

A sleazy and unethical tabloid reporter for the National Tattler who has a history of harassing Will Graham. He sensationalizes active investigations for profit, often obstructing police work and endangering lives in his pursuit of a scoop.

An independent and spirited blind woman who works at the same film processing lab as Francis Dolarhyde. Unaware of Dolarhyde's dark secret, she becomes his love interest and offers him a glimpse of a normal life that conflicts with his "Dragon" persona.