FormerpolicedetectiveAdrianMonk(TonyShalhoub),whosephotographicmemoryandamazingabilitytopiecetogethertinycluesmadehimalocallegend,hassufferedfromintensifiedobsessive-compulsivedisorderandavarietyofphobiassincetheunsolvedmurderofhiswife,Trudy,in1997.NowonpsychiatricleavefromtheSanFranciscoPoliceDepartmentandworkingasafreelancedetective/consultantondifficultcases,Monkhopestoconvincehisformerboss,CaptainLelandStottlemeyer(TedLevine),toallowhimtoreturntotheforce.Stottlemeyer,whowaveredbetweenadmirationforMonkandannoyanceathiseccentricitiesduringthefirstseason,isbecomingmoreofafriendtoMonkastheseriesdevelops,frequentlycallinghimintohelp,asmuchforMonk'sbenefitasforhisown.However,heknowsMonk'slimitationsaswellashisstrengthsandmaystillharbordoubtsaboutthewisdomofallowingMonktocarryagunorsubdueaperpetrator.Stottlemeyer'ssecond-in-command,LieutenantRandallDisher(JasonGray-Stanford),alsoseemstobedevelopingbothadmirationandcompassionforthemanheoncelabeled"thedefectivedetective." Despiteflawsandinadequaciesallaround,thethreearebecominganincreasinglyeffectiveteam,withadditionalhelpfromMonk'spersonalassistant.Fromthedouble-episodepilotthroughthefirsthalfofseasonthree,Monkwasaidedbyhisnurse,SharonaFleming(BittySchram).Butinthetenthepisodeofthethirdseason,Sharonawasreplacedbyanewassistant,NatalieTeeger(TraylorHoward).LikeSharona,adivorceewithasonnamedBenjy,Natalieisasingleparent,awidowwithadaughternamedJulie(EmmyClarke).UnlikeSharona,Natalieisnotanursebutaformerbartenderwithafreshperspectiveon"Mr.Monk,"asshestilladdresseshernewboss.
妻子的死让警探艾德里安（托尼·夏尔赫布TonyShalhoub饰）的生活跌落到了谷底，不久之后，常常陷入悲痛之中的艾德里安患上了强迫症。强迫症令艾德里安在警局里无处容身，很快，他便丢掉了工作，成为了无业游民。 为了生存，艾德里安必须赚钱，就这样，一家私人侦探所成立了。艾德里安雇佣了护士莎罗纳（BittySchram饰）为他打理日常生活，自己则靠着出色的逻辑推理能力和过目不忘的神奇本领解决了一件又一件离奇案件。之后，艾德里安结识了名为娜塔莉（特蕾勒·霍华德TraylorHoward饰）的单身母亲，两人之间十分投缘。随着时间的推移，丧妻之痛由浓转淡，但妻子被害一案的前因后果却依然深藏在迷雾之中，艾德里安能够依靠自己的力量破解此案揭开心结吗？
