Janine Ditullio, a Massachusetts native, began her career as a stand-up comedian, performing at Boston venues like Catch a Rising Star and the Comedy Studio. She also appeared at New York City's Spin Cycle Comedy evenings in the late 1990s.

Ditullio broke barriers as the first woman writer for The Jon Stewart Show (1994) and Late Night with Conan O'Brien (1995-2001), contributing to the nightly monologue. She later wrote for Late Night with Jimmy Fallon (2010) and served as writing director for Superjail! (2012). Her writing credits also include Metalocalypse and My Kind of Town. She is best known for voicing Paula Small in the cult classic animated series Home Movies (1999-2004) and also wrote seven episodes for the show.

Ditullio co-executive produced My Kind of Town and founded Chirpbug, an interactive online technology. Her work has earned her two Writers Guild of America Awards and six Emmy nominations.