| •Christine Lahti | played | Dr. Kate Austin (Episodes 31-119, recurring otherwise) |
| •Adam Arkin | played | Dr. Aaron Shutt |
| •Alan Rosenberg (2) | played | Stu Brickman (Episodes 134-141, recurring otherwise) |
| •Barbara Hershey | played | Dr. Francesca Alberghetti (Episodes 120-141) |
| •Carla Gugino | played | Dr. Gina Simon (Episodes 120-141, recurring otherwise) |
| •E. G. Marshall | played | Dr. Arthur Thurmond (Episodes 1-13) |
| •Eric Stoltz | played | Dr. Bobby Yeats (Episodes 98-119) |
| •Hector Elizondo | played | Dr. Phillip Watters |
| •James Garner | played | Hugh Miller (2000) |
| •Jamey Sheridan | played | Dr. John Sutton (Episodes 28-45) |
| •Jayne Brook | played | Dr. Diane Grad (Episodes 23-119, recurring otherwise) |
| •Lauren Holly | played | Dr. Jeremy Hanlon (Episodes 120-141) |
| •Mandy Patinkin | played | Dr. Jeffrey Geiger (Episodes 1-30, 120-141, recurring otherwise) |
| •Mark Harmon (1) | played | Dr. Jack McNeil (Episode 46 - 141) |
| •Peter Berg | played | Dr. Billy Kronk (Episodes 23-119, recurring otherwise) |
| •Peter MacNicol (1) | played | Alan Birch (Episodes 1-30, recurring otherwise) |
| •Rocky Carroll | played | Dr. Keith Wilkes (Episodes 46-141) |
| •Roma Maffia | played | Angela Giandamenicio (Episodes 1-13) |
| •Roxanne Hart | played | Camille Duschene Shutt (Episodes 1-45, recurring otherwise) |
| •Stacy Edwards | played | Dr. Lisa Catera (Episodes 76-119) |
| •Thomas Gibson (2) | played | Dr. Danny Nyland (Episodes 14-71, recurring otherwise) |
| •Vondie Curtis-Hall | played | Dr. Dennis Hancock (Episodes 23-119, recurring otherwise) |
