Monk is extremely flattered when Hollywood star David Ruskin is chosen to play him in a movie. However, the actor begins to take this role a little too seriously, and not only does he begin taking on Monk's mannerisms, but soon begins to believe that he's actually Monk. Meanwhile, Monk has other things on his plate, investigating two different murder cases, which he soon learns may be related to each other.

When the San Francisco sanitation workers go on a garbage strike, it leaves the entire city littered with garbage. Mr. Monk is appalled by the situation and wants nothing more than to have his city cleaned. When the union boss is suddenly founded dead, with his death being ruled a suicide, Mr. Monk begins to investigate. With reason to believe that his death was a homicide, Mr. Monk must get to the bottom of the suspicious case if he ever wants to live in a clean city again.

When Julie's basketball coach is found dead in the shower, seemingly electrocuted by accident, the authorities accept the easy explanation. However, Julie and her teammates think otherwise and hire Monk to find out what really happened. Meanwhile, Natalie acts as replacement coach to Julie's team, and recruits a hesitant Monk to be her assistant. Monk, who has never won anything in his life, wants nothing more than the team to win, so that he can get his first trophy.

Monk is at the local firehouse getting his smoke alarms examined, but an intruder murders a firefighter and blinds Monk when he throws a solvent onto his face. At first Monk has trouble coping with the fact that he's lost his eyesight, but soon realizes how much happier he is now that he isn't able to see all the filth surrounding him.

Monk is practically forced to open up his own private detective agency across town, because of Natalie and her persistent ways. Their first case is a woman who wants the culprit who hit her car found. At first, Monk isn't very enthusiastic about this lackluster case, but after some probing, he soon realizes that it's tied to another murder case that the police are looking into.

Monk is excited about his 25-year college reunion, where he has fond memories of meeting Trudy. But when a nurse is found dead, and all signs point to the killer being someone in attendance at the reunion, Monk's trip down memory lane turns into a murder investigation.

Monk's overworked therapist retires after the murder of his cleaning lady, which puts the defective detective in a tight spot. When he can't bear to find a replacement shrink, he works hard to solve the crime.

Monk and Natalie look for Stottlemeyer's truant son at a rock concert, but they end up with a murder investigation on their hands when a roadie is found dead in a portable toilet.

While celebrating Christmas with Natalie, Monk receives quite a surprise when his estranged truck-driver father, Jack, whom Monk hasn't seen in 39 years, comes to town. When Monk decides to accompany his dad on a cross-country route, they soon find out that a partner in Jack's company is missing and that Jack's truck may hold some interesting clues.

Monk has been hired by a millionaire to recover some papers from his estate, but soon he found himself in the middle of a murder plot.

Monk is positively giddy when he makes a new friend, but Natalie and the others are convinced that the overly amiable guy isn't what he seems.

When a wealthy couple are killed, Monk poses as a butler at their sprawling abode to investigate. He ends up working for their son, a filthy rich brat who has had a longtime crush on Natalie. Along the way, Monk discovers he's afraid of frogs and that his meticulous nature serves him well as a manservant.

Biederbeck later appears funneling information to Monk about Trudy's murder in "Mr. Monk Goes to Jail" (2.16) and "Mr. Monk Is On the Run (Part Two)" (6.16). At the end of this episode Dale "The Whale" Biederbeck loses his pocket politician, the Lieutenant Governor, during a failed conspiracy to assassinate the Governor. Biederbeck is left destitute and powerless for the remainder of his sentence.

Disher retires to run a farm that he inherits from a dead uncle. But when he suspect foul play in his relative's death, he calls in Monk

Dr. Charles Kroger, portrayed by Stanley Kamel, is Monk's psychiatrist during the first six seasons of the show. On April 8, 2008, Stanley Kamel died of a heart attack in between production of seasons six and seven.[5] His character was said to have died of a heart attack as well when Monk restarted in the season 7 episode "Mr. Monk Buys a House". The episode was dedicated to his memory.

Mitch, her late husband, was shot down over Kosovo in 1998. She first appeared in "Mr. Monk and the Red Herring" (3.10).[3][4] She is also the narrator of a series of novels based on Monk and written by Lee Goldberg. Lieutenant Randy Disher, portrayed by Jason Gray-Stanford, is a lieutenant in the Homicide Division of the SFPD.