- Steve Martin Stu Preissler
- Jack Black Brad Harris
- Owen Wilson Kenny Bostick
- Brian Dennehy Raymond
- Anjelica Huston Annie Auklet
- Rashida Jones Ellie
- Rosamund Pike Jessica
- Dianne Wiest Brenda
- John Cleese Narrador
- Kevin Pollak Jim Gittelson
- Joel McHale Barry Loomis
- JoBeth Williams Edith Preissler
- Paul Campbell Tony
- Barry Shabaka Henley Dr. Neil Kramer
- Jim Parsons Crane