- Scott Thompson - Brian
- Jeremy Piven - Jerry Capen
- Kathryn Harrold - Francine Sanders
- Winona Ryder - Winona Ryder
- David Spade - David Spade
- John Hoffman - David
- Bruno Kirby - Bruno Kirby
- Jennie Garth - Jennie Garth
- Tom Arnold - Tom Arnold
- Richard Frank - Thomas
- Richard Lewis - Richard Lewis
- Robert Hays - Robert Hays
- Ian Buchanan - Jonathan Litman
- Helen Hunt - Helen Hunt
- Elizabeth Ashley - Elizabeth Ashley
- French Stewart - Intern
- Farrah Fawcett - Farrah Fawcet
- Drew Barrymore - Drew Barrymore
- Carl Reiner - Carl Reiner
- Jason Alexander - Jason Alexander
- Larry Miller - Larry Miller
- William Shatner - William Shatner
- Robin Williams - Robin Williams
- Kathy Kinney - Dog Trainer
- Danny DeVito - Danny DeVito
- Tim Allen - Tim Allen
- Lea Thompson - Herself
- Bob Costas - Bob Costas
- Andy Williams - Andy Williams
- Bob Saget - Bob Saget
- Pat Sajak - Pat Sajak
- Frederick de Cordova - Fred De Cordova (as Fred De Cordova)
- Peter Falk - Peter Falk
- Alec Baldwin - Alec Baldwin
- Jon Lovitz - Jon Lovitz
- Daniel Baldwin - Daniel Baldwin
- Phil Hartman - Phil Hartman
- Corbin Bernsen - Corbin Bernsen
- Jeff Chayette - Larry's Look-a-like
- Kathy Ireland - Kathy Ireland
- Bella Shaw - Bella Shaw
- Bobcat Goldthwait - Bobcat Goldthwait
- David Letterman - David Letterman
- Ray Wise - Lloyd Simon
- Jimmie Walker - Jimmie Walker
- George Wendt - George Wendt
- David Duchovny - David Duchovny
- Elvis Costello - Elvis Costello
- Sally Field - Sally Field
- Sting - Sting
- Jake Johannsen - Jake Johannsen
- Ellen DeGeneres - Ellen DeGeneres
- Kevin Nealon - Kevin Nealon
- Todd Barry - Todd Barry
- Carol Burnett - Carol Burnett
- Steve Duchesne - Steve Duschesne
- Dana Carvey - Dana Carvey
- Jeff Cesario - Jeff Cesario
- Michael Richards - Michael Richards
- Mimi Rogers - Mimi Rogers
- George Foreman - George Foreman
- Billy Crystal - Billy Crystal
- Catherine O'Hara - Catherine O'Hara
- Richard Simmons - Richard Simmons
- Ray Combs - Ray Combs
- Earl Holliman - Earl Holliman
- Hugh Hefner - Hugh Hefner
- Sugar Ray Leonard - Sugar Ray Leonard
- Roseanne Barr - Roseanne Barr
- Jay Leno - Jay Leno
- George Segal - George Segal
- Ed Begley Jr. - Ed Begley Jr.
- Sarah Silverman - Wendy Traston
- Sarah Silverman - Sarah Silverman
- Jeff Goldblum - Jeff Goldblum
- Gina Gershon - Gina Gershon
- Illeana Douglas - Illeana Douglas
- Laura Dern - Laura Dern
- Jerry Stiller - Jerry Stiller
- Heidi Klum - Heidi Klum
- Drew Carey - Drew Carey
- Michael Bolton - Michael Bolton
- Eriq La Salle - Eriq La Salle
- Tom Snyder - Tom Snyder
- Steven Wright - Steven Wright
- Anita Barone - Michelle
- Suzanne Somers - Suzanne Somers
- Joan Embery - Joan Embery
- Eric Bogosian - Stan Paxton
- Patrick O'Connell - Patrick O'Connell
- Gary Kemp - Jake Woodward
- Talia Balsam - Talia Balsam
- Alex Trebek - Alex Trebek
- Ed McMahon - Ed McMahon
- Adam Sandler - Adam Sandler
- Leah Lail - Leah Lail
- Roger Eschbacher - Man
- Katherine Olsen - Sharon
- Peter Tolan - Adam Loderman
- Maureen Mueller - Kiki Rosatti
- Warren Zevon - Warren Zevon
- Joshua Malina - Joshua Malina
- Gene Siskel - Gene Siskel
- John Ritter - John Ritter
- Burt Reynolds - Burt Reynolds
- Jerry Seinfeld - Jerry Seinfeld
- Martin Mull - Martin Mull
- Robin Quivers - Robin Quivers (voice)
- Bob Odenkirk - Stevie Smith
- Howard Stern - Howard Stern
- Chris Farley - Chris Farley
- Deborah May - Melanie Parrish
- Rif Hutton - Executive
- Cindy Morgan - Karen Jackson
- Steve Kehela - David's Pal
- Sheila Shaw - Kingsley's Queen #2
- Lisa Amsterdam - Carol's Assistant
- Hervé Villechaize - Hervé Villechaize
- James Karen - Sheldon Davidoff
- Carmen Filpi - Bert Crawley
- Kimberley Kates - Sally
- Jeff Arbaugh - Kyle The Associate Director
- Sam Whipple - Makeup Artist
- Shashawnee Hall - Security Guard
- Lisa Cloud - Focus Group Member
- Mindy Sterling - Writer
- Jeanne Basone - Cindy Remington
- David Paymer - Norman Litkey
- Suanne Spoke - Carol Biederman
- Tom Dahlgren - Ben Smalley
- Dana Delany - Dana Delany
- John Riggi - Reporter
- Kristin Davis - Bri
- Jack Shearer - Jack
- Laura Leighton - Herself
- Angie Dickinson - Angie Dickinson
- Sarah Jessica Parker - Self
- Kevin Steinberg - Stagehand
- Rosie Shuster
- Victor Levin
- Brad Grey
- Adam Resnick
- Maya Forbes
- Steven Levitan
- Jeff Cesario
- Judd Apatow
Danny DeVito interpreta a Danny DeVito en la serie.
Sarah Jessica Parker interpreta a Self en la serie.
Peter Falk interpreta a Peter Falk en la serie.
Ellen DeGeneres interpreta a Ellen DeGeneres en la serie.
Sally Field hace el papel de Sally Field.
Lea Thompson hace el papel de Herself.
Carl Reiner hace el papel de Carl Reiner.
Robin Williams hace el papel de Robin Williams.
Winona Ryder interpreta a Winona Ryder en la serie.
Garry Shandling interpreta a Larry Sanders en la serie.
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