前警探阿德里安·蒙克（托尼·沙尔胡布饰）过目不忘，惊人的拼凑微小线索的能力使他成为当地的传奇人物，自从妻子特鲁迪（Trudy）被谋杀未解决后，他就患有严重的强迫症和各种恐惧症， 1997 年。 现在，从旧金山警察局休精神病假，并在疑难案件中担任自由侦探/顾问，蒙克希望说服他的前任老板利兰·斯托特迈耶上尉（泰德·莱文饰）允许他重返警队。Stottlemeyer 在第一季对蒙克的钦佩和对他的古怪行为的烦恼之间摇摆不定，随着系列的发展，他越来越成为蒙克的朋友，经常打电话给他提供帮助，这既是为了蒙克的利益，也是为了他自己的利益。然而，他知道僧侣的局限性和长处，并且可能仍然怀疑允许僧侣携带枪支或制服肇事者的智慧。斯托特迈耶的二把手兰德尔·迪舍中尉（杰森·格雷-斯坦福饰）似乎也对这个他曾经称为“有缺陷的侦探”的人产生了钦佩和同情。
尽管存在缺陷和不足之处，但在蒙克私人助理的额外帮助下，三人正在成为一支越来越高效的团队。从双集试播到第三季前半段，蒙克得到了护士莎罗娜·弗莱明（Bitty Schram）的帮助。但在第三季第十集中，莎罗娜被新助理娜塔莉·泰格（特雷勒·霍华德饰）取代。和离婚的莎罗娜一样，娜塔莉是一个单亲父母，寡妇，女儿名叫朱莉（艾美克拉克）。与莎罗娜不同，娜塔莉不是一名护士，而是一名前调酒师，对“蒙克先生”有着全新的看法，因为她仍在向她的新老板讲话。
Former police detective Adrian Monk (Tony Shalhoub), whose photographic memory and amazing ability to piece together tiny clues made him a local legend, has suffered from intensified obsessive-compulsive disorder and a variety of phobias since the unsolved murder of his wife, Trudy, in 1997. Now on psychiatric leave from the San Francisco Police Department and working as a freelance detective/ consultant on difficult cases, Monk hopes to convince his former boss, Captain Leland Stottlemeyer (Ted Levine), to allow him to return to the force. Stottlemeyer, who wavered between admiration for Monk and annoyance at his eccentricities during the first season, is becoming more of a friend to Monk as the series develops, frequently calling him in to help, as much for Monk's benefit as for 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 both 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. From the double-episode pilot through the first half of season three, Monk was aided by his nurse, Sharona Fleming (Bitty Schram). But in the tenth episode of the third season, Sharona was replaced by a new 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.
