- Benjamin Bratt - Jake Reilly
- Brian Benben - Sheldon Wallace
- Griffin Gluck - Mason Warner
- Sarah Drew - Judy
- Kimberly Elise - Angie Paget
- Joey Luthman - Evan P. Dawson
- Chris Gartin - Keith Embry
- Leslie Hope - Linda
- Billy Dee Williams - Henry
- Amy Acker - Molly Madison
- Hallee Hirsh - Melissa
- Sean O'Bryan - Dave Walker
- Geoffrey Blake - Jack Grossman
- Marin Hinkle - Beverly
- Ming-Na Wen - Kara Wei
- Abigail Spencer - Rachel
- Joel Grey - Dr. Alexander Ball
- Fran Kranz - Brian
- Josh Randall - Carl
- Stacey Travis - Paige Merring
- James Pickens Jr. - Dr. Richard Webber
- Amanda Detmer - Morgan Gellman
- Tamlyn Tomita - Katie's Lawyer
- Grant Show - Dr. Archer Forbes Montgomery
- Hannah Marks - Ruby
- Stephen Ford - Fillmore 'Dink' Davis
- Mimi Kennedy - Eleanor Bergin
- Idina Menzel - Lisa King
- George Newbern - Dr. Brian Reynolds
- Patrick Dempsey - Dr. Derek Shepherd
- Holliston Coleman - Tess Sullivan
- Rebecca Mader - Leslie
- Ivar Brogger - Ronald Debray
- George Segal - Wendell Parker
- Alexandra Holden - Laura Larson
- Siena Goines - Claudia Jenkins
- Ann Cusack - Susan Grant
- Dinah Lenney - Mrs. Hobart
- John Getz - Mr. Kent
- Melissa McCarthy - Lynn McDonald
- Ever Carradine - Kara
- Darby Stanchfield - Tess Milford
- Amber Benson - Jill Avery
- Dorian Harewood - Duncan Stinson
- Ione Skye - Monica Daniels
- Marguerite Moreau - Lynn Jarvis
- Molly Hagan - Karen Adams
- Keiko Agena - Sister Amy
- Tyler Patrick Jones - Dean Miller
- Tom Amandes - Charlie Jensen
- Susan May Pratt - Barbara
- Susan Ruttan - Nora
- Jonathan Goldstein - Rabbi
- David Newsom - John Burton
- Agnes Bruckner - Heather Parker
- Sharon Leal - Sonya Nichols
- Alyssa Shafer - Patty
- Rebecca Lowman - Nicole Tisch
- Corey Reynolds - Ray Paget
- Nina Siemaszko - Kathleen
- Mageina Tovah - Rebecca Hobart
- Geoffrey Arend - Jimmy
- Tom Irwin - Father Mark
- Stacy Edwards - Maria Wilson
- Alexis Denisof - Daniel Larson
- Brett Cullen - Allan
- Erik Palladino - Mitch Thompson
- Gina Ravera - Dawn
- Ernie Hudson - Captain Frank
- Justin Chambers - Dr. Alex Karev
- Diane Venora - Sharon
- Rosanna Arquette - Corinne Davis
- Valerie Mahaffey - Marilyn Sullivan
- Robin Weigert - Amelia Sawyer
- Andy Milder - Doug Adams
- Blake Robbins - Mark Miller
- Jennifer Westfeldt - Jen Harmon
- Amanda Foreman - Katie Kent
- Joe Nieves - Greg
- Moon Unit Zappa - Jenny
- Bess Wohl - Amy Larson
- Rosalind Chao - Lillie Jordan
- Devon Gummersall - Ronald Bergin
- David Sutcliffe - Kevin Nelson
- Brennan Elliott - Jake
- Gordon Clapp - Coach Mike
- Joy Jorgensen - Darcy
- Scott Michael Campbell - Gregory Milford
- Miles Heizer - Michael
- Stephen Collins - Montgomery
- JoBeth Williams - Bizzy Forbes
- Carl Gilliard - Desk Officer
- Josh Hopkins - Noah Barnes
- Chandra Wilson - Dr. Miranda Bailey
- Debra Mooney - Sylvie
- Ellery Sprayberry - Sasha
- Cullen Douglas - Hal Jarvis
- Joan McMurtrey - Jennifer Debray
- Wayne Wilderson - Neil Delhom
- Leonard Roberts - Ryan
- Parisa Fitz-Henley - Cami Davis
- Suzy Nakamura - Margaret Delhom
- Karley Scott Collins - Erin
- Jay Harrington - Dr. Wyatt Lockhart (uncredited)
- Emma Caulfield Ford - Leanne Thompson
- Steven W. Bailey - Joe
- Rebecca Field - Rachel Gold
- Ben Shenkman - Rob Harmon
- Cristián de la Fuente - Dr. Eric Rodriguez
- David Giuntoli - Daniel Woods
- Chyler Leigh - Dr. Lexie Grey
- Chris McGarry - Michael
- Aloma Wright - Mildred
- Emily Rios - Angela Reilly
- Lucy Hale - Danielle
- Charlie McDermott - Bobby Douglas
- Porter Kelly - Sharon
- Major Curda - Toby
- Jackson Odell - Max (uncredited)
- Patricia Lentz - Judge
- Joshua Rush - Will
- David Mazouz - Marshall Rakoff
- Tessa Thompson - Zoe Salter
- Sara Rue - Shira Cole
- Rockmond Dunbar - Jacob Deever
- Eric Dane - Dr. Mark Sloan
- Nathan Gamble - Cody
- Clea DuVall - Natasha
- Michael Grant - Patrick Hoffman
- Ava Gaudet - Stacey Meyer
- Julie Ann Serrano - Hospital Patient (uncredited)
- Julie Ann Serrano - Pregnant Teen (uncredited)
- Theo Stockman - Wes
- Sarah Lieving - Actress
- Bruce Purcell - Doctor (uncredited)
- Phoebe Tonkin - Hailey
- Rachel G. Fox - Missy Spencer
- Tom Virtue - Dr. Warren
- Amy Farrington - Lisa Nussbaum
- Debby Ryan - Hailey
- Christinna Chauncey - Trish
- Daniel Kash - Officer Hanson
- Matt Long - James Peterson
- Aaron Ashmore - Carl
- Jolie Jenkins - Producer
- Michelle Wong - Sheila
- Richard Roundtree - Raymond McCray
- Kenneth Mitchell - Elliott
- Ajarae Coleman - Hot Waitress
- Clare Carey - Pam Tanner
- Zoe Perry - Lisa
- Kylie Rogers - Sarah Nelson
- Jack Axelrod - Oscar Schmitt
- JT Mollner - Bartender
- Tisha Campbell - Pam Reiter
- Carter MacIntyre - Nick Calhoun
- Justina Machado - Stephanie Kemp
- Missy Yager - Megan Stewart
- Charlie Hofheimer - Ron Nelson
- Chryssie Whitehead - Dana Nelson
- Steve Zissis - Todd Reiter
- Angela Bullock - Clara
- Karen Lew - Triage Nurse
- Tony Edwards - Security Guard
- Betsy Beers
- Mark Tinker
- Chris Van Dusen
- Mark Gordon
- Shonda Rhimes
Ione Skye interpreta a Monica Daniels en la serie.
Tamlyn Tomita hace el papel de Katie's Lawyer.
Rosanna Arquette interpreta a Corinne Davis en la serie.
Billy Dee Williams hace el papel de Henry.
Stephen Collins interpreta a Montgomery en la serie.
Kate Walsh interpreta a Addison Montgomery en la serie.
Paul Adelstein interpreta a Cooper Freedman en la serie.
KaDee Strickland hace el papel de Charlotte King.
Caterina Scorsone interpreta a Amelia Shepherd en la serie.
Taye Diggs hace el papel de Sam Bennett.
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