[9] Joffe was responsible for Holofcener's first "real" job in the movie industry: a production assistant on Woody Allen's A Midsummer Night's Sex Comedy in 1982.

Holofcener's first experiences with film as a child left her either frightened or sad; she recalled her fright at Jerry Lewis's The Nutty Professor.

Holofcener originally wanted to become an artist like her father, but felt she wasn't as talented as others in her classes at Sonoma State University.

[17] Holofcener made her feature film writing and directing debut in 1996 with Walking and Talking, which starred Catherine Keener, Anne Heche, Todd Field, Liev Schreiber, and Kevin Corrigan.

[22] Her understanding of modern, professional women made her an ideal choice to direct female-centric television shows like Sex and the City, Leap of Faith and Gilmore Girls.

[23] Featuring performances by Catherine Keener, Brenda Blethyn, Emily Mortimer and newcomer Raven Goodwin, the film was not only critically acclaimed[12] but did well at the box office.

[citation needed] After directing two episodes of the series Six Feet Under, Holofcener began work on her third film, Friends with Money, which featured Jennifer Aniston, Joan Cusack, Frances McDormand, and Catherine Keener.

[25] The film also gained Holofcener a nomination with the Writers Guild of America Awards for Best Original Screenplay.

[9][13] The film also features Oliver Platt, Rebecca Hall, Amanda Peet, and Sarah Steele.

In 2015, it was announced that Holofcener was set to direct an adaptation of Lee Israel's memoir Can You Ever Forgive Me?, with Julianne Moore in the lead role.