A situation comedy centered on Caroline Duffy, a young cartoonist living in the Tribeca neighborhood of New York City. Each episode begins with a brief animated sequence reflecting the autobiographical nature of her syndicated newspaper cartoon strip Caroline in the City, explicitly compared with the real comic strip Cathy in several episodes. The first season hinged on the complicated romantic relationship between Caroline and Del, a divorced hunk with commitment problems, and a slowly evolving, understated romantic attraction between Caroline and Richard, her cynical colorist who, as a aspiring painter, is embarrassed by his job and at first resists becoming entangled in Caroline's personal life but slowly realizes he is falling in love with her. Comic relief is provided by Caroline's neighbor and best friend Annie, a professional dancer trapped in the endless run of Cats and an endless succession of unsuccessful relationships with men, and Del's bizarre underling Charlie.  The series ran for four years.

Matthew Perry appears in 'Caroline and the Folks' as Chandler Bing, could he be any more crossed over?