- Kevin Fonteyne - Derrick Wells
- Jonathan Silverman - Dr. John Lieberman
- Tara Summers - Allison McDaniels
- Mason Cook - Quinn McDaniels
- Eyal Podell - Mark Ridgeway
- Anthony Giangrande - Dr. Thomas Ottobrini
- Matt Crabtree - Gordon Willis
- Cara Pifko - Beth Hostetler
- Nija Okoro - Aisha Ali
- Kevin Shinick - Levi Hostetler
- Sonya Eddy - Joanne Whitman
- Sharon Muthu - Dr. Sharika Kumar
- Blake Robbins - Dr. David Martin
- Laura Richardson - Nurse Veronica Woolward
- Robb Reesman - Surgeon Leigh Durrell
- Patrick Quinlan - EMT
- Betsy Baker - Mrs. Sutcliff
- Lou Volpe - Mr. Sutcliff
- Rachael Drummond - Mrs. Wilson
- Jonny Lee - James
- Cozi Zuehlsdorff - Trisha Miller
- Valerie Dillman - Yvonne Miller
- Bradley White - Owen Miller
- Del Hunter-White - Mrs. Jasper
- Elena Campbell-Martinez - Mariah Gonzales
- Ewan Chung - Doctor Wong
- Ewan Chung - Wong
- Eden Riegel - Sandy Slade
- Rusty Burns - Gladys
- Jason Gray-Stanford - Atty. Scott Henderson
- Burl Moseley - Technician
- Adam Rose - Joe Newton
- Gian Franco Tordi - Gianni
- Anthony Heald - Mitch Tompkins
- Valerie Mahaffey - Fran Horowitz
- Raphael Sbarge - Mr. Cooper
- Arabella Field - Marilyn Cooper Kupcheck
- Dale Raoul - Eloise Fernwood
- Rakefet Abergel - Carla
- Jill E. Alexander - Anesthesiologist
- Mike Grief - Floyd Fernwood
- Cat Hammons - Psych Ward Nurse
- Adrian Quinonez - Paramedic
- Kaelyn Raye Lustig - Emma Cooper
- Lou Saliba - Male Patient
- Devon Bostick - Benjamin Decada
- Samantha Hanratty - Abra Rivers
- Meeghan Holaway - Priscilla Rivers
- Dean Cudworth - Lionel Rivers
- Alexandra Bokyun Chun - Mrs. Park
- Zylan Brooks - ER Nurse
- Ryan McCartan - Daniel
- Jeff Clarke - Frank Valente
- Hal Holbrook - Dr. Arvin Wayne
- Annika Marks - Tory Britton
- Matthew Yang King - Tsung Mai
- Rob Brownstein - Transplant Surgeon
- Denzel Whitaker - Nick Villanueva
- Charlie Bodin - Glenn Kubiak
- Sage Mears - Morgan Britton
- Jeremy Denzlinger - Paramedic
- Wendy Haines - Scrub Nurse
- Sarah Hudson - Circulating Nurse
- Reiley McClendon - Jacob Gold
- Holley Fain - Kara Bishop
- Wilmer Calderon - Mike Garrett
- Derek Mio - Alex Kimura
- Whitney Avalon - Lori Newton
- Dave Engfer - Dr. Mac Ryan
- Ioan Gruffudd - Dr. Stewart Delany
- Lukas Behnken - Keith Harriman
- Rhonda Aldrich - Ms. Harriman
- Tim Martin Gleason - Dan Ford
- Yvonne Caro Caro - Elena Cabrera
- Marcos De Silvas - Fernando Cabrera
- Maya Goodwin - Anesthesiologist
- Johnny Kostrey - Paramedic
- Nicole Pettis - Paramedic
- Jon Schmidt - Paramedic
- A.J. Tannen - Anesthesiologist
- Megan Gallagher - Ms. Wells
- Bonnie Bailey-Reed - Ellen Coolidge
- Akeem Mair - Family Visitor
- Akeem Mair - Chef
- William Charlton - George Coolidge
- Sumalee Montano - Lynne Iverson
- John Burke - News Anchor
- Mercedes Ruehl - Judge Beverly Natheson
- Anna Moon - Respiratory Therapist
- Kenneth Mitchell - Asher Knox
- Spencer Daniels - Gregory Malloy
- Cleo Berry - Darryl Fisher
- Denise Dowse - Mrs. Fisher
- Harry S. Murphy - Judge
- Bashir Gavriel - Paramedic Roth
- Carmella Riley - Nurse Gladys Doise
- Bill D'Elia
Alexandra Bokyun Chun interpreta a Mrs. Park en la serie.
Mercedes Ruehl interpreta a Judge Beverly Natheson en la serie.
Ving Rhames interpreta a Dr. Jorge Villanueva en la serie.
Jamie Bamber interpreta a Dr. Tyler Wilson en la serie.
Jennifer Finnigan interpreta a Dr. Tina Ridgeway en la serie.
Bill Irwin interpreta a Dr. Buck Tierney en la serie.
Keong Sim interpreta a Dr. Sung Park en la serie.
Sarayu Blue interpreta a Dr. Sydney Napur en la serie.
Emily Swallow interpreta a Dr. Michelle Robidaux en la serie.
Alfred Molina hace el papel de Dr. Harding Hooten.
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