Monk is shadowed by an actor intending to play a fictional version of him, but the actor's presence soon has some repercussions for one of Monk's real-life cases.
A union boss' death threatens to prolong a city-wide garbage strike in San Francisco. It's up to Monk to help end the strike by determining whether the boss' death was suicide or murder.
Julie's high school basketball coach dies in an apparent accident, but Julie and her friends suspect murder. Monk suspects the girls are right, so he and Natalie take the case...and also take over the basketball team as Coach and Assistant Coach.
At a firehouse, Monk loses his eyesight when an unidentified man kills a retired fireman and then throws solvent into his eyes. He must then try and help solve the murder case, while dealing with the fact that he may ever see again.
Natalie, feeling inspired, convinces Monk to become a for-hire private eye. On their first case, they get stuck investigating a fender bender which, surprisingly, leads them to a murder case.
Monk attends his twenty-fifth college reunion hoping to have fun, but instead must investigate the murder of a former university nurse. Monk soon realizes that the murderer is one of his former classmates, and he must stop him before he kills again.
Dr. Kroger's cleaning lady is killed in his office. He believes one of his patients must have killed her, and therefore he decides to retire. In order to get him to go back to work, Monk must solve the case.
Captain Stottlemeyer's son skips school to go to a rock concert, and Monk and Natalie go with the captian to search for him. While they are there, a roadie turns up dead of what looks like a drug overdose. Monk decides to investigate.
Monk's truck driving father, whom he hasn't seen in thirty-nine years, asks to see Monk when he gets arrested for a traffic violation. After Monk gets him out of jail, Monk joins his father on the road while he does some drop-offs for Christmas. He learns he has a half brother that he's never met. Soon the two find themselves trying to solve a strange mystery together.
A millionaire with leprosy wants to hire Monk. Monk does not even want to be near him, but Natalie convinces him he should take the case after meeting with leprocy expert Dr. Polanski. Soon, the simple case becomes a shadowy murder plot suitable for a film noir.
Monk meets an overly friendly guy named Hal at the grocery store. Hal invites Monk to a hockey game. Natalie is immediately suspicious of him. Meanwhile, a woman that Monk used to carpool with is found dead after arriving home from a trip to Europe.
Natalie hires Monk to investigate the deaths of her parents' wealthy neighbors. Natalie believes their son Paul may have been involved. Monk, who hasn't had any work recently, takes the job. He must go undercover as a butler to get close to Paul.
A woman is found dead in her house. The police believe she left her gas fireplace on, took a nap, and died of asphyxiation. Her sister hires Monk, who soon believes that her husband, shock jock Max Hudson, was involved in her death.
Lt. Disher inherits a farm from an uncle who committed suicide. After botching up a drug raid, he decides to quit the police force and start a new life as a farmer. Soon, Disher starts to suspect that his uncle was murdered, so he calls Monk and asks for help.
The mysterious "Six Way Killer" strikes a street musician and Monk and the team are put together with a federal agents and their flashy gadgets. However, Monk starts to believe that a case that looks unrelated is the key to solving the crime, not technology.
Monk gets a bloody nose. He goes to the emergency room with Natalie, who soon leaves him to go on a date. A doctor in the hospital winds up dead, so Monk joins the murder investigation. Soon, his own life is in grave danger.