After the death of his wife Trudy Anne Monk (1962-97) who was killed by a car bomb, Monk began to fall apart. He got fired from his job as detective with the San Francisco police when he began to manifest an Obsessive Compulsive Disorder (OCD). Until he can get his anxiety problems under control, he won‘t be able to return to active duty. Meanwhile, Monk hires himself as a private consultant and uses his detective skills to solve crimes.

Monk's attention to detail and his Zen/Sherlock Holmes like demeanor enables him to read people and the environment, to see what others do not. Monk’s talisman is a set of keys that belonged to his wife’s car. He holds them close until he can discover the true facts behind her death. Monk occasionally will play his clarinet at the foot of his wife’s grave.

Monk’s sidekick is a practical nurse named Sharona Fleming (Bitty Schram) who monitors Monk's progress and helps him cope with stressful situations. For instance, when Monk walks down the street, he will compulsively begin to touch and count each and every parking meter he passes. And meal time has a strict order: Tuesday is always chicken pot pie night. When Sharona moved back to New Jersey, Monk hired Natalie Teeger (Traylor Howard) as his new assistant. See also "Monk, Adrian"