- Jana Marie Hupp - Jesse
- Ken Sagoes - Byron
- Vivica A. Fox - Sarah
- John Cho - Lucas Bender
- Natasha Leggero - Mindy
- Will Sasso - Russ
- Christine Dunford - Vicki
- Valerie Harper - Barbara Stark
- Kevin Nealon - Stephen Redford
- Miriam Flynn - Bonnie Woodcock
- Nick Bakay - Karl
- Jessica Lundy - Barbara
- Mitch Longley - Joe
- Bill Fagerbakke - Terence
- Johann Urb - Greg
- Gilbert Gottfried - Tommy
- Barry Bostwick - George Von Stuessen
- Kevin Farley - Steve
- Victor Raider-Wexler - Marshall Duffy
- Dan Butler - Paul
- Krysten Ritter - Allison Stark
- Richard Lewis - Miles Tunnicliff
- Mayim Bialik - Dr. Bialik
- Ken Jeong - Dr. Park
- Wendie Malick - Dr. Friedman
- Brandon Soo Hoo - Ernie
- Bill Farmer - George Bush / Minister (voice)
- Kelly Perine - Doctor
- Margaret Cho - Nicole
- Lucas Grabeel - Pete Pratt
- Jerry Adler - Al Stark
- Susan Yeagley - Simona
- Lenny Clarke - Mr. Donnelly
- Mackenzie Foy - Little Girl
- Ted McGinley - Webby
- Tricia Leigh Fisher - Denise
- Alan Thicke - Alan Thicke
- Haley Pullos - Kid (uncredited)
- Alison La Placa - Beth
- K Callan - Mrs. Bauer
- Maree Cheatham - Mrs. Wallach
- Elaine Tan - Julie
- Clarence Clemons - Self
- Jerry Lambert - Stan
- George Wyner - Rabbi
- Dioni Michelle Collins - Counter Attendant #2
- Julie Claire - Ilene
- Stephen Lee - Bob
- Alan Oppenheimer - Mr. Wallach
- Meeghan Holaway - Gwen
- Martin Mull - Mr. White
- Martin Mull - Whitey
- Anthony Anderson - Cofeld
- Ashley Greene - Waitress
- Lainie Kazan - Donna
- Kym Whitley - Tina
- Tom Parker - Ryan
- Jill-Michele Meleán - Hockey Girl
- Eric Unger - Jeremy
- Anzu Lawson - Lisa
- Kate Micucci - Ally
- Timm Sharp - Doug Von Stuessen
- Laura Clery - Allison Stark
- Noureen DeWulf - Dina
- Matt Champagne - Professor Dubowski
- Michael Mitchell - Alex
- Stephanie Pearson - Missy
- Aree Davis - Girl #1
- Josh Goldsmith
- Cathy Yuspa
Vivica A. Fox hace el papel de Sarah.
Brad Garrett hace el papel de Eddie Stark.
Joely Fisher interpreta a Joy Stark en la serie.
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