- Nicole Sullivan - Deirdre Bishop
- Michael Boatman - Ted Elliot
- Tori Spelling - Roxanne Fiedler
- Bob Odenkirk - Colin Hunter
- Pamela Anderson - Vicki Devorski
- Vanessa Evigan - Sandy
- Giuliana Rancic - Journalist
- Noel Gugliemi - Marco
- Tracy Hutson - Tracy Hutson
- Julie Claire - Receptionist
- Michael Burger - Man
- Jerry Lambert - Dr. Altman
- Lucy Lawless - Tracy Fletcher
- French Stewart - Gene Schmidtline
- Michael Angarano - George Denton
- Star Jones - Dr. Curtis
- Barry Bostwick - Max Damarius
- Cynthia Preston - Monique
- Nikki Ziering - Gloria
- Kat Dennings - Kaitlin
- Paula Abdul - Kathleen
- Kimberly Williams-Paisley - Laura
- Anne Dudek - Annie
- Christopher Knight - Waiter
- Vincent Pastore - Bookie
- Ali Hillis - Tiffany
- Randee Heller - Mrs. Ross
- Danny Bonaduce - Ron
- Caroline Aaron - Roz
- Esther Scott - Interviewer
- Eddie McClintock - Jake Heberling
- Kristin Bauer - Kaye Buchinski
- Josh Braaten - Charlie
- Pat Finn - Luke McNamara
- Carole Davis - Mrs. Butler
- Joey McIntyre - Ethan
- Bill Walton - Bill Walton
- Joanna Cassidy - Norma
- Joanna Kerns - Judy, Owen's Other Mom
- John DiMaggio - Bartender
- Joan Rivers - Louise
- Martin Mull - Buddy
- Connie Ray - Nona
- Brooke Burke - Nurse Benson
- Jenny McCarthy-Wahlberg - Dani
- George Wyner - Alan Turnbach
- Beth Stern - Joelle
- Harry Groener - Dr. Lars Skaarsgard
- Ben Feldman - Nicholas
- Danielle Bisutti - Sales Lady
- Rolando Molina - Security Man
- Sean Whalen - Phillip
- Mo Collins - Toni St. George
- Richard Ruccolo - Bobby Casey
- William Ragsdale - Mitch Calgrove
- Erik Palladino - Mike Abrejo
- Masi Oka - Hideki
- Lesley Ann Warren - Diane Steadman
- John McEnroe - John McEnroe
- Diana Maria Riva - Vivian
- Joe Liss - Dr. Stokely
- Simon Helberg - Arthur
- Valerie Harper - Judith, Owen's Mom
- David Cassidy - Vince
- Regis Philbin - Xin Xao Pi
- Chris Gartin - Trevor
- Stephen Lee - Store Owner
- Gordon Clapp - Detective Martin
- Kathryn Joosten - Old Lady
- Mark Curry - Morpheus
- Tinsley Grimes - Penny
- Cindy Williams - Joan
- Mike Randleman - Waiter
- Darrell Alston - Piano Player
- Jim Rash - Rob McLyle
- John O'Brien - Executive
- Jonathan Bray - Delivery Guy
- Benjamin King - Tom
- Zaid Farid - Security Guard
- Steven Basil - Guy
- Angela Sargeant - Trina
- Joleen Lutz - Instructor
- Janiece Jary - Preschool teacher
- Lawrence LeJohn - Executive
- Joseph G. Medalis - Older Executive
- Sean Moran - Party Guy
- John Eric Bentley - Assistant Director
- Stefan Marks - Stage Manager
- Mike Siegel - New Potato Guy
- Jennifer Echols - Cafeteria Worker
- DJ Rabiola - Bouncer
- Janell Inez - Saleswoman
- J.P. Manoux - Peter
- Howard S. Miller - Executive
- Don Calfa - Uncle Nicky
- Vernard 'Bone' Hampton - Bakery Clerk
- Ana Rey - Assistant
- Alex Craig Mann - Waiter
- Todd Tongen - Reporter
- Marcy Goldman - Female Employee
- Martin Papazian - Delivery Person
- David Weisenberg - Male Employee
- Jonathan Tipton Meyers - Maitre D'
- Suzanne Kent - Madeline
- Jim Belushi - Eddie Smirkoff
- Gil Zuniga - Nello
- Gil Zuniga - Norm
- Bryan Callen - Peter
- Dondré Whitfield - William
- Stephanie Childers - Jane
- Andrew Hunter Sherman - Wyatt
- Jon Collins - Office Worker
- Pat Dade - Cashier
- Will Friedle - Caleb
- Jane Edith Wilson - Customer
- Alissa Dean - Genie
- Chris Hogan - Andrew
- Ricky Reidling - Paramedic
- Richard Kind - Lance Corcoran
- Joseph Stephens Jr. - Feeler
- Simon Harvey - Hotel Manager
- Darlene Kardon - Mavis
- Christopher T. Wood - Photographer
- Sonya Eddy - Security Woman
- Carole Goldman - Saleswoman Marie
- Jim O'Heir - Russell
- Bruce Dent - Art Critic
- Natasha Alam - Daniella
- David Muller - Man
- Alex Skuby - Fran
- Alexandra Ackerman - Bridget
- James McMann - Bar Patron
- Tony Plana - Owl Inspector
- Lawrence Gilliard Jr. - Chester
- Anthony Liebetrau - Man in Line
- Charles C. Stevenson Jr. - Earl
- Ezra Godden - Justin
- Terry Hughes
- Ted Wass
- Rob LaZebnik
- Christine Zander
- Chuck Tatham
- Sarah Jane Cunningham
- Claudia Lonow
- Steve Holland
Sara Rue hace el papel de Claude Casey.
Sherri Shepherd interpreta a Ramona Platt en la serie.
Andrea Parker interpreta a Lydia Weston en la serie.
Zachary Levi interpreta a Kipp Steadman en la serie.
Patrick Warburton interpreta a Jeb Denton en la serie.
Andy Dick interpreta a Owen Kronsky en la serie.
Will Sasso hace el papel de Carl Monari.
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