Adrian Monk (Tony Shalhoub) was once a rising star with the San Francisco Police Department, legendary for using unconventional means to solve the department's most baffling cases. But after the tragic (and still unsolved) murder of his wife Trudy, Monk developed an extreme case of obsessive-compulsive disorder.  Now consumed by peculiar obsessions and wracked with hundreds of phobias (including but certainly not limited to germs, heights, and even milk), Monk has lost his badge and struggles with even the simplest everyday tasks.

Despite his many quirks, Monk is fortunate to have some supportive friends. With the help of his gifted therapist Dr. Kroger (Stanley Kamel), Monk has made some gradual progress in controlling his condition. Monk's first personal assistant, Sharona Fleming (Bitty Schram), was able to help him pick up the pieces of his life and get back to doing what he does best: solving crimes. Though Monk was devastated when she moved away, he soon found hope in the form of a spunky new assistant, Natalie Teeger (Traylor Howard), whose unique brand of tough love proved to be just what Monk needed. In Natalie, Monk has found more than just an assistant; she's a faithful friend, a savvy businesswoman, and, it turns out, a pretty good assistant detective to boot. Natalie and her teenage daughter Julie (Emmy Clarke) have welcomed Monk into their family. And though Natalie and Monk have grown close, she's never afraid to give her boss a loving kick in the pants when he needs it.

Now working as a private consultant, Monk continues to investigate cases in the most unconventional ways. Although Monk is no longer a member of the police force, his former boss Captain Leland Stottlemeyer (Ted Levine) still often calls upon him to provide unique insights into cases that have the cops stumped. Stottlemeyer himself is a highly decorated detective, but he knows he will never be as good as the illustrious Monk... and it drives him crazy. Still, he's a loyal friend to Monk, as is Lieutenant Randall Disher (Jason Gray-Stanford) the Captain's self-appointed go-to guy, a cop with enough eagerness to almost make up for his lack of brilliance as a detective.

Monk is a detective afraid of the dark, a gumshoe afraid of gum. He has no problem cracking a case - as long as it doesn't involve heights or germs, and is in close proximity to his apartment. Other than solving his wife's murder, Monk would like nothing more than to gain back his position on the San Francisco police force, but can he pull himself together and get back to solving crimes full time?