| Noah Wyle | John Carter |
| Maura Tierney | Abby Lockhart |
| Mekhi Phifer | Gregory Pratt |
| Goran Visnjic | Luka Kovac |
| Sherry Stringfield | Susan Lewis |
| Parminder Nagra | Neela Rasgotra |
| Linda Cardellini | Samantha Taggart |
| Shane West | Ray Barnett |
| Laura Innes | Kerry Weaver |
| Mädchen Amick | Wendall Meade |
| Eion Bailey | Jake Scanlon |
| Pat Carroll | Rebecca Chadwick |
| Louise Fletcher | Roberta 'Birdie' Chadwick |
| Arlen Escarpeta | Adrian |
| Scott Grimes | Archie Morris |
| Laura Cerón | Nurse Chuny Marquez |
| Troy Evans | Frank Martin |
| Montae Russell | Dwight Zadro |
| Yolanda Lloyd Delgado | Elena Tabajas |
| Judyann Elder | Debra Graham |
| James Molina | Santiago Tabajas |
| Frederick Koehler | Benjamin Coe - Legal Aid Attorney |
| Verda Bridges | May Crawford |
| Jarrod Bunch | Corrections Officer Carranza |
| Dawnnie Mercado | Marta |
| Ivo Nandi | Emilio |
| Rob Narita | Ed Miyamoto |
| Moira Price | Liza |
| David Di Brienza | X-Ray Technician |
| Thandiwe Newton | Makemba 'Kem' Likasu |