On October 5, 2004, Amy Sedaris and Paul Rudd participated in a reading of director/writer Adrienne Shelly's screenplay, Waitress, at 6:30pm at the East 13th Street Theater (136 East 13th Street, between 3rd and 4th Avenues). Admission was free, and a party followed at Duke & Duchess (65 4th Avenue, between 9th and 10th Streets). The reading was staged by WET (Women's Expressive Theater) and also starred Michael Cerveris, Gretchen Mol, Sasha Eden, Nathan Dean, James McCaffrey, Chuck Montgomery, Merritt Wever, and Lisa Zambetti.

The story is a quirky tale about a waitress named Jenna who makes and serves the best pies that anyone in her small southern town has ever tasted. Every day she creates a new concoction, inspired by her life's daily occurrences and named accordingly. The problem is that she hates her husband and she wants out, but she recently and inconveniently discovered that she's pregnant. Things get more complicated when she embarks upon an affair with her new obstetrician.

Amy read the role of Becky, one of Jenna's pie-serving sidekicks.

Near the end of 2005, the screenplay went before the cameras, but with an almost entirely different cast (Nathan Dean appeared in both the staged reading and the film). The film was adored by critics and starred Keri Russell as Jenna, Jeremy Sisto as her husband Earl, Nathan Fillion as Dr. Pomatter, Cheryl Hines as Becky (the role Amy played during the reading), Andy Griffith as Old Joe, and Adrienne Shelly herself as Dawn. Also featured were Sarah Hunley as Dr. Mueller, Eddie Jemison as Ogie, Darby Stanchfield as Francine Pomatter, and Lew Temple as Cal. Unfortunately, the film's writer/director/co-star Adrienne Shelly never got the chance to enjoy her success. After the film was completed, but before it was released, Shelly was murdered. Her film survives as a testament to her talent. Cheryl Hines and Andy Griffith get the biggest laughs and Keri Russell is the cutest woman on the big screen since Audrey Tautou in Amelie and Jennifer Garner in 13 Going On 30.