- Ron Glass - Derrial Book
- Damion Poitier - Henchman
- Tom Towles - Lund
- Andrew Bryniarski - Crow
- Gregg Henry - Sheriff Bourne
- Doug Savant - Commander Harken
- Branden R. Morgan - Survivor
- Lancer Dean Shull - Radio Operator
- Benito Martinez - Boss
- Erik Passoja - Bree
- Bob Fimiani - Elder Gommen
- Daniel Bess - Mudder
- Kevin Gage - Stitch Hessian
- Zachary Kranzler - Fess Higgins
- Edward Atterton - Atherton Wing
- Larry Drake - Sir Warwick Harrow
- Larry Pennell - Murphy
- William Converse-Roberts - Gabriel Tam
- John Thaddeus - Stark
- Gary Werntz - Patron
- Andy Rolfes - Marcus Grange / Older Grange
- Blake Robbins - Agent McGuinness
- Tom Virtue - Pompous Doctor
- Roma Chugani - Receiving Doctor
- Katherine Kendall - The Councillor
- Rolando Molina - Bolles
- Michael Bentt - Viktor
- Richard Brooks - Jubal Early
- Andy Umberger - Dortmunder Captain
- Philip Sternberg - Inara's Client
- Colin Patrick Lynch - Radio Operator
- Bonnie Bartlett - Patience
- Domingo Vara - Ensign
- Jeff Ricketts - Man
- Jeff Ricketts - Blue Glove Man #1
- Dennis Cockrum - Blue Glove Man #2
- Dennis Cockrum - Other Man
- Stephen O'Mahoney - Dortmunder Man
- John F. Kearney - Old Man
- Valerie Red-Horse - Deputy
- Kevin Will - Officer
- Eric Lange - Fed
- David Reynolds - Henchman
- Rene Hamilton - Immigrant Woman
- Clement Blake - Mudder Elder
- John Jabaley - Bartender
- Jordan Lund - Foreman
- Bob McCracken - Well-Dressed Man
- Laura Niemi - Woman
- Simon Brooke - Prod
- Michael McMillian - Younger Hopeful
- Kim Onasch - Banning
- Janora McDuffie - Cabott
- Roy Werner - Gentleman
- Erica Tazel - Doralee
- Cate Cohen - Crash Team Nurse
- John Dunn - The Torturer
- Skylar Roberge - Young River
- Eddie Adams - Bendis
- Zac Efron - Young Simon
- Rick Williamson - Bar Guy, Henchman (uncredited)
- Gary J. Wayton - Rebel Soldier (uncredited)
- Heath Russell - Background (uncredited)
- Heather Crawford - Mud Man (uncredited)
- Tiffany Michelle - Mudwoman (uncredited)
- Joshua Grenrock - Porter
- Joel Steingold - Head Cop
- Ron Ostrow - Commander
- Kelli Wheeler - Blue Sun Spokesmodel (uncredited)
- Adam Pilver - Vanilla Husband (scenes deleted)
- Johnny Shakespeare - Torture Victim
- Jamie McShane - Man
- Michael Keyes - Sleeping Soldier (uncredited)
- Greg Wendell Reid - Crying Soldier (uncredited)
- Rabatan Salem - Hoodlum (uncredited)
- Brian J. Williams - Two Fry (uncredited)
- Gerard J. Reyes - Bodyguard / Shopper (uncredited)
- Mark Sheppard - Badger
- Steven Flynn - Captain Sash
- Ilia Volok - Marco
- Lyle Kanouse - Salesman
- Dax Griffin - Bester
- Roderick McCarthy - Lacey #1
- Christina Hendricks - Saffron
- Ben Edlund
- Joss Whedon
- Tim Minear
Benito Martinez interpreta a Boss en la serie.
Gregg Henry hace el papel de Sheriff Bourne.
Nathan Fillion interpreta a Mal Reynolds en la serie.
Gina Torres interpreta a Zoë Washburne en la serie.
Alan Tudyk hace el papel de Hoban Washburne.
Morena Baccarin interpreta a Inara Serra en la serie.
Adam Baldwin hace el papel de Jayne Cobb.
Jewel Staite interpreta a Kaylee Frye en la serie.
Sean Maher interpreta a Simon Tam en la serie.
Summer Glau hace el papel de River Tam.
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