Adrian Monk (Tony Shalhoub) is a former police detective who suffers from obsessive-compulsive disorder and various phobias. He was once known as a local legend due to his photographic memory and ability to piece together tiny clues. Since the unsolved murder of his wife, Trudy, in 1997, he has been on psychiatric leave from the San Francisco Police Department and working as a freelance detective/consultant on difficult cases.
Captain Leland Stottlemeyer (Ted Levine) is Monk's former boss and is becoming more of a friend to him as the series develops. He frequently calls in Monk to help, both for Monk's benefit and his own. However, he knows Monk's limitations as well as his strengths and may still harbor doubts about the wisdom of allowing Monk to carry a gun or subdue a perpetrator.
Stottlemeyer's second-in-command, Lieutenant Randall Disher (Jason Gray-Stanford), also seems to be developing admiration and compassion for the man he once labeled "the defective detective."
Despite flaws and inadequacies all around, the three are becoming an increasingly effective team, with additional help from Monk's personal assistant, Natalie Teeger (Traylor Howard). Like Sharona, a divorcee with a son named Benjy, Natalie is a single parent, a widow with a daughter named Julie (Emmy Clarke). Unlike Sharona, Natalie is not a nurse but a former bartender with a fresh perspective on "Mr. Monk," as she still addresses her new boss.