- Erika Alexander - Pam Tucker
- Joseph C. Phillips - Martin Kendall
- Joseph C. Phillips - Daryl
- Merlin Santana - Stanley
- Sinbad - Davis Sarrette
- Christine Andreas - Hairdresser
- Blair Underwood - Mark
- Deon Richmond - Kenny
- Carl Anthony Payne II - Cockroach
- Wallace Shawn - Jeffrey Engels
- Roscoe Lee Browne - Dr. Barnabus Foster
- Karen Malina White - Charmaine Brown
- Sônia Braga - Anna Maria Westlake
- Essence Atkins - Paula Young
- Max Roach - Dr. Gordon Darton
- Sullivan Walker - Dr. James Harmon
- Chandra Wilson - Dina
- Stacey Dash - Michelle
- Lisa Vidal - Mrs. Miron
- Ted Ross - Dean Harris
- Ed Lover - Taxi Driver
- Freda Foh Shen - Cliff's Patient
- Steve Whitmire - Scallions (voice)
- Raphael Sbarge - Mr. Jenkins
- Danny Kaye - Dr. Burns
- Earle Hyman - Russell Huxtable
- Earle Hyman - Voice of MacBeth (uncredited)
- Rita Moreno - Mrs. Granger
- E.G. Marshall - Stanley Rappaport
- Leslie Uggams - Kris Temple
- Bern Nadette Stanis - Carolyn Thompson
- Sheldon Leonard - Dr. Wexler
- Tracey Ross - Fran
- Betty Carter - Amanda Woods
- Don Franklin - Greg Martinson
- Edmund Lyndeck - Mr. Bingham
- Mario Van Peebles - Garvin
- Eve Gordon - Glenda
- Iona Morris - Veterinarian
- John Amos - Dr. Herbert
- Robbi Chong - Doctor
- Ann Flood - Mrs. Kenton
- Rosalind Cash - Dr. Hughes
- Norman Beaton - Carleton
- Al Freeman Jr. - Coach Ernie Scott
- Stevie Wonder - Stevie Wonder
- Kristoff St. John - David James
- Keith Reddin - Mr. McManis
- Louis Nye - Norman Kirby
- Eileen Heckart - Mrs. Hickson
- Tichina Arnold - Delores
- Lela Rochon - Veronica
- Judith Jamison - Marie
- Arnold Stang - Man in Waiting Room
- Adam Sandler - Smitty
- LaChanze - Sylvia
- Ann Reinking - Jill Kelly
- CCH Pounder - Clair's friend
- Miriam Makeba - Self
- Meg Foster - Dyan
- Alan North - Judge
- Doris Belack - Saleswoman
- J. August Richards - Roy
- Daryl Mitchell - Old Head
- Terry Farrell - Nicki Phillips
- Kadeem Hardison - Phillip Washington
- Elaine Stritch - Mrs. McGee
- Amy Yasbeck - Alicia Evans
- Lisa Mordente - Expectant Mother
- Russell Nype - Mr. Traugett
- Debbie Allen - Emma
- Jason Bernard - Sgt. Major Boswell Stokes
- Minnie Gentry - Aunt Gramtee
- Mercedes Ruehl - Bernadette Foley
- Tonya Pinkins - Iris
- William Christian - Mr. Robertson
- Saundra Quarterman - Lisa Hairston
- Charles Brown - Capt. Turvey
- Debbi Morgan - Tracy
- Harold Perrineau - Scott
- Samuel E. Wright - Dr. Dan Morgan
- Joe Williams - Al Hanks
- Allen Payne - Lance Rodman
- Victoria Rowell - Paula
- Rachel True - Nicki
- Eugene Byrd - Eugene
- Dick Vitale - Dan Vicente
- Ethel Ayler - Carrie Hanks
- Robin Givens - Susanne
- Lou Myers - Mr. Davis
- Kasi Lemmons - Miss McKegney
- Troy Winbush - Denny
- Mavis Staples - Soloist
- Kathleen Doyle - Paula
- Gilbert Gottfried - Mr. Babcock
- John Ritter - Ray Evans
- Joe Seneca - Dr. Zachariah J. Hanes
- Gabrielle Carmouche - Deirdre Arpelle
- Clayton Prince - Eddie Lakehart
- Marge Redmond - Mrs. Lebeau
- Alec Mapa - Wretched Fan
- Nancy Wilson - Lorraine Kendall
- L. Scott Caldwell - Elizabeth
- Clarice Taylor - Anna Huxtable
- Joel Fabiani - Richard
- B.B. King - Riley Jackson
- Suzzanne Douglas - Rebecca Shorter
- Anthony Quinn - Mr. Fuentes
- Melba Moore - Patricia Abbott
- Plácido Domingo - Alberto Santiago
- Austin Pendleton - Mr. Kensington
- Lisa Rieffel - Susan Hennings
- Audrey Landers - Cookie Bennett
- Tony Orlando - Tony Castillo
- Carl Ballantine - The Great Ballantine
- Dave Goelz - The Great Gonzo / Digit (voice)
- Seth Gilliam - Aaron Dexter
- Alicia Keys - Maria
- Roger Robinson - Mitch Lawson
- Lynne Thigpen - Mrs. Hudson
- Pamela Blair - Karen
- Angela Bassett - Sara
- Gloria Foster - Dr. Barbara Bracy
- Dub Taylor - Slim Claxton
- Lena Horne - Lena Horne
- Naomi Campbell - Julia
- Red Buttons - Jake Bennett
- Malinda Williams - Shana
- Malinda Williams - Althea Logan
- Richard Lawson - Mr. Bostic
- Patricia Richardson - Mrs. Schrader
- Russell Curry - Tad
- Kevin Kilner - Steve
- Noel MacNeal - Cheese (voice)
- Bill Irwin - Eddie Bartholomew
- Denise Nicholas - Lorraine
- Troy Byer - Ellen
- Leila Kenzle - Girl
- Christopher Plummer - Jonathan Lawrence
- Alexis Cruz - Enrique Tarron
- Steven Culp - Father-to-Be
- Paulene Myers - Pauline
- Michelle Thomas - Justine Phillips
- Moses Gunn - Dr. Lotus
- Moses Gunn - Joe Kendall
- Leila Danette - Mrs. Whitaker
- Reno Wilson - Howard
- Carmen Finestra - Andy Witherspoon III
- Carmen Finestra - Mr. Fuentes's Son
- S. Epatha Merkerson - Elena
- Robert Weil - Mike
- Eagle-Eye Cherry - Guy
- Dondré Whitfield - Robert
- Mushond Lee - Slide
- Gary LeRoi Gray - Nelson Tibideaux
- William Thomas, Jr. - Dabnis Brickey
- Maurice Lauchner - Herman
- Pam Potillo - Janet
- Elizabeth Narvaez - Kara
- Nicole Leach - Davina
- Nicole Leach - Danielle
- Marcella Lowery - Francine Tibideaux
- Phyllis Yvonne Stickney - Phyllis
- Robert Culp - Scott Kelly
- Clarence Williams III - Mr. Thornehill
- Todd Hallowell - Denise's Friend
- Marilyn Rockafellow - Mrs. Burke
- Dizzy Gillespie - Mr. Hampton
- Jossie DeGuzman - Mrs. Ramos
- Anne Twomey - Mrs. Jennings
- Clarke Gordon - Mr. Halifax
- Doug Yasuda - Steve Yamado
- Haru Aki - Janet Yamado
- Tzi Ma - Mr. Lee
- Suzee Pai - Mrs. Lee
- Aleta Mitchell - Mrs. Randall
- Elisa de La Roche - Nurse
- Donald McKayle - Ralph
- Christine Langner - Girl
- Iman - Mrs. Montgomery
- Kim Hauser - Melissa
- Shawn Elliott - Mr. Wilson
- Lloyd Battista - Lawyer
- Robert King - Dr. Mike Newcomb
- Ada Maris - Selena Cruz
- David Langston Smyrl - Sam Lucas
- David Langston Smyrl - Man in Court
- David Langston Smyrl - Chester
- Olga Merediz - Mrs. Rodriguez
- Victoria Gabrielle Platt - Tori
- Ron Foster - Herb Temple
- Ron Foster - Mr. Hanson
- Paul Harding - Mr. Kenton
- Jeff Mooring - Greg
- George Grizzard - Mr. Barker
- Anne DeSalvo - Miss Kessler
- Liliana Głąbczyńska - Clair's Assistant
- Ahmad Rashād - Quiz Show Announcer (voice)
- Ahmad Rashād - Rodeo Announcer (voice)
- Lauren Tom - Mrs. Gwynne
- Edythe Jason - Woman
- Shari Headley - Mrs. Dubois
- Matt Williams - Jack Westlake
- Eileen Letchworth - Betty
- Art Blakey - Drummer
- Jimmy Heath - Saxophonist
- Tito Puente - Timbal Player
- Josephine Premice - Mrs. Cunningham
- Lorraine Morin-Torre - Assistant
- Bill Gunn - Homer
- Tanya Wright - Tanya
- Leonard Jackson - Exterminator
- Eddie Castrodad - Gerald
- Eden Svendahl - Professor Grayson
- Eden Svendahl - Officer Harrison
- Diane Lozada - Nina
- Tico Wells - Jerry
- Ray Baker - Mr. Schrader
- Wendy Gazelle - Mrs. Gregory
- Lee Weaver - Waiter
- Lee Weaver - Mr. Fields
- Nan-Lyn Nelson - Nancy
- Michael Vale - Mr. Lee
- Alvin Lum - Mr. Howe
- Carla Brothers - Shower Guest
- Claude Brooks - Donnie
- Claude Brooks - Donny
- Susan Diol - Cheryl
- Douglas Turner Ward - Mark
- Vanessa Williams - Jade
- Vanessa Williams - Cheryl
- Omar Torres - Hector
- Pam Grier - Samantha
- Conrad McLaren - Judge
- Ronald Yamamoto - Mr. Ogawa
- Marina Durell - Estelle Drake
- Robert Gossett - Stage Manager
- Dennis Singletary - Lyle Thompson
- Angelina Fiordellisi - Pamela
- Alva Chinn - Mrs. Roscoe
- Alva Chinn - Alex
- Alva Chinn - Expectant Mother
- Christopher Collet - Jake Palmer
- Gwen McGee - Nurse
- Erica Gimpel - Jennifer
- Josh Pais - Andy
- Kevin Rock - Ted
- Traci Wolfe - Teresa
- Traci Wolfe - Terri
- Michele Shay - Nicole Harmon
- Jodi Long - Jo Ann
- Colin Quinn - Davey Herbeck
- Laurie Morrison - Lindy Harmon
- Wynonna Smith - Denise's Friend
- Sari Chang - Nurse Young
- Grace Johnston - Carolyn Gregory
- Edouard DeSoto - Mr. Rueter
- Mary B. Ward - Mrs. Jenkins
- Akili Prince - Cal
- Akili Prince - Scott
- Hazel Medina - Sheila
- Carole Shelley - Barbara
- Diana Georger - Clerk
- Michael Lombard - Mr. Benedict
- Richard Gant - Moving Man
- Alex Ruiz - Lou Hernandez
- Richard Scanlon - Gary
- Billy 'Sly' Williams - Lenny
- Amy Hunter - Amy
- Sammy Davis Jr. - Ray Palomino
- Leticia Herrera - Louisa Sanchez
- Heather Coleman - Party Guest
- Tiger Haynes - Coach Barry
- Birdie M. Hale - Mrs. Barry
- Bill Bradley - Men's Basketball Player
- Dave DeBusschere - Men's Basketball Player
- Nancy Lieberman - Women's Basketball Player
- BarBara Luna - Cynthia
- Don Reed - Mitchell
- Frank Adu - Police Officer
- Spike Alexander - Glen
- Keith Diamond - Danny
- Royana Black - Patsy
- Wanakee Legardy - Secretary
- Raynor Scheine - Bob
- Chris Griggs - Nelson Tibideaux
- Tatyana Ali - Girl
- Shaun Weiss - Boy
- Avanti Taylor - Amy
- Lanny Flaherty - George
- Joanna Rhinehart - Tori
- Brenda Braxton - Judy
- Fran Brill - Pink Frackle / Patina / Tomato (voice)
- Richard Hunt - Statler / Blue Frackle / Sandwich (voice)
- Jim Martin - Doglion / Cauliflower (voice)
- David Rudman - Sweetums / Boo Monster (voice)
- Garland Whitt - Elliott
- Danielle Burgio - Emcee
- Danielle Burgio - Waitress
- Kharisma - Preschool Girl
- Kharisma - Partygoer
- Gilbert Cruz - Andy
- Jonathan Halyalkar - Jonathan
- Jonathan Halyalkar - Partygoer
- Sandman Sims - Self
- Nicholas Sadler - Thief
- L.B. Williams - Auctioneer
- Richard Woods - Steve Parnell
- Ernest Abuba - George Parker
- Ray DeMattis - Alfred Phelps
- Ray DeMattis - Auction Telephone Representative
- Yamil Borges - Julia Arroyo
- David Ilku - Guy
- Cynthia Bailey - Sheniquah Watkins
- Jackie Roberts - Nancy
- Shellye Broughton - Ms. Dobbs
- Maureen Sadusk - Nurse
- Clebert Ford - Mr. Atkins
- Jerome Dempsey - Dave
- Olivia Ward - Mrs. Fields
- Carlton Beener - Marlon
- Kenneth Meseroll - Jonathan Rappaport
- Twinkle Burke - Waitress
- Blaire Whitney - Leslie Engels
- Jeff Williams - Ben
- Eddie Robinson - Dan
- Phil Nee - Delivery Guy
- John Lantz - Sportscaster / Announcer (voice)
- Damien Leake - Andy Anderson
- Lucy Martin - Gwen Graham
- Eugene Williams - Tim
- Rosanna Carter - Rosanna
- Lili Bernard - Mrs. Minifield
- Joseph A. Halsey - Pizza Delivery Person
- David López - Luis
- Daphne Maxwell Reid - Millicent
- Margaret Avery - Leah
- Willie Colón - Willie Colón
- Raymond Anthony Thomas - Commencement Announcer
- Kennan Scott - Rahim
- Grace Garland - Maxine
- Elayne Boosler - Dr. Strauss
- Tom Werner
- Marcy Carsey
- Caryn Mandabach
- Elliot Shoenman
- John Markus
- Matt Williams
S. Epatha Merkerson interpreta a Book Club Member #5 en la serie.
Bill Cosby hace el papel de Heathcliff Huxtable.
Phylicia Rashād hace el papel de Clair Huxtable.
Malcolm-Jamal Warner interpreta a Theo Huxtable en la serie.
Tempestt Bledsoe interpreta a Vanessa Huxtable en la serie.
Keshia Knight Pulliam hace el papel de Rudy Huxtable.
Sabrina Le Beauf hace el papel de Sondra Huxtable.
Geoffrey Owens interpreta a Elvin Tibideaux en la serie.
Raven-Symoné hace el papel de Olivia Kendall.
Erika Alexander hace el papel de Pam Tucker.
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