- Ian Somerhalder - Boone Carlyle
- Cynthia Watros - Libby Smith
- Jeff Fahey - Frank Lapidus
- Harold Perrineau - Michael Dawson
- Henry Ian Cusick - Desmond Hume
- Nestor Carbonell - Richard Alpert
- ??? - Sun-Hwa Kwon
- Daniel Dae Kim - Jin-Soo Kwon
- Rebecca Mader - Charlotte Lewis
- Adewale Akinnuoye-Agbaje - Eko Tunde
- Maggie Grace - Shannon Rutherford
- Ken Leung - Miles Straume
- Zuleikha Robinson - Ilana Verdansky
- Emilie de Ravin - Claire Littleton
- Kiele Sanchez - Nikki Fernandez
- Rodrigo Santoro - Paulo
- Michael Emerson - Benjamin Linus
- Michael Emerson - Henry Gale
- Saul Rubinek - Clark Finney
- Charles Mesure - Bryan
- Alan Dale - Charles Widmore
- Kevin Tighe - Anthony Cooper
- Dan Gauthier - Peter Ross
- Andrew Divoff - Mikhail Bakunin
- William Mapother - Ethan Rom
- Zack Shada - Liam Pace
- Stephanie Niznik - Evelyn Ariza
- Dariush Kashani - Haddad
- Tamara Taylor - Susan Lloyd
- Kim Dickens - Cassidy Phillips
- William Atherton - Donald Reynolds
- Kristin Richardson - Jessica
- David S. Lee - Charles Widmore
- James Horan - Wayne
- Katey Sagal - Helen Norwood
- Brett Cullen - Goodwin Stanhope
- Adetokumboh M'Cormack - Yemi
- Reiko Aylesworth - Amy Goodspeed
- Raymond J. Barry - Ray Shephard
- Julie Ow - Nurse
- Donnie Keshawarz - Essam Tasir
- Nick Tate - Ray Mullen
- Clancy Brown - Kelvin Inman
- Skye McCole Bartusiak - Kate Austen
- Susan Gibney - Melissa Dunbrook
- Jim Piddock - Francis Heatherton
- Steven Elder - Jonas Whitfield
- Anthony Azizi - Omar Idris
- ??? - Decorator
- Michael DeLuise - David
- Nick Jameson - Richard Malkin
- Julie Bowen - Sarah Wagner
- Jeff Perry - Frank Duckett
- Evan Handler - Dave
- Ian Gomez - Munson
- Oliver Muirhead - Monsignor
- Justin Chatwin - Eddie Colburn
- Lana Parrilla - Greta
- Cheech Marin - David Reyes
- Wayne Pygram - Isaac of Uluru
- Beth Broderick - Diane Janssen
- John Simon Jones - Travel Agent
- Zack Ward - Marc Silverman
- Paula Malcomson - Colleen Pickett
- Andrew Connolly - Brother Campbell
- Keir O'Donnell - Thomas
- Scott Paulin - Sullivan
- Swoosie Kurtz - Emily Locke
- Shawn Doyle - Duncan Forrester
- Rachel Ticotin - Teresa Cortez
- Jon Gries - Roger Linus
- Jenny Gago - Alyssa Cole
- Jodi Lyn O'Keefe - Ava
- Mirelly Taylor - Isabella
- Anson Mount - Kevin
- Sammi Davis - Mrs. Pace
- Monica Bârlădeanu - Gabriela Busoni
- Neil Hopkins - Liam Pace
- Chris Mulkey - Mike
- Kevin Dunn - Gordy
- Brittany Perrineau - Mary Jo
- Lindsay Frost - Sabrina Carlyle
- Tony Lee - Jae-Young Lee
- Melissa Farman - Danielle Rousseau
- Shishir Kurup - Donovan
- Lawrence Mandley - Frainey
- Zeljko Ivanek - Edmund Burke
- Robert Frederick - Jeff
- Dayo Ade - Justin
- Fredric Lehne - Edward Mars
- Ron Bottitta - Leonard Simms
- Carter Jenkins - Tom Brennan
- Gabrielle Fitzpatrick - Lindsey Littleton
- Chad Donella - Desk Clerk
- Stewart Finlay-McLennan - Laurence
- June Kyoto Lu - Mrs. Paik
- Suzanne Krull - Lynn Karnoff
- Patrick Fischler - Phil
- Andrea Roth - Harper Stanhope
- April Grace - Bea Klugh
- Marc Casabani - Tariq
- Frederick Koehler - Seamus
- Craig Robert Young - Commercial Director
- Ronald Guttman - Angelo Busoni
- Veronica Hamel - Margo Shephard
- Michael Bowen - Danny Pickett
- Shaun Toub - Sami
- Mackenzie Astin - Tom Brennan
- Billy Dee Williams - Self
- Tom Connolly - Jones
- James Huang - Chet
- Chris Jaymes - Doctor
- Geoff Heise - Doctor
- Hakeem Kae-Kazim - Emeka
- James Lesure - Rob Hamill
- Nathan Fillion - Kevin Callis
- Jeff Kober - Mechanic
- Robert Patrick - Hibbs
- Doug Hutchison - Horace Goodspeed
- Thekla Reuten - Elsa
- Marguerite Moreau - Starla
- Grant Bowler - Captain Gault
- Josh Randall - Nathan
- Brooke Anderson - Charlotte
- Saïd Taghmaoui - Caesar
- Vanessa Branch - Karen
- Julie Adams - Amelia
- Diana Scarwid - Isabel
- Jacob Witkin - Howard Zukerman
- Michelle Ruff - Jane
- Dean Norris - Howard Gray
- Tom Irwin - Dan Norton
- Alexandra Krosney - Ellie
- Sebastian Siegel - Erik
- Kevin Rankin - Jerry
- Rebecca Hazlewood - Nalini
- Rick Overton - Matthew Reed
- Brian Goodman - Ryan Pryce
- Bill Duke - Warden Harris
- Kevin Chapman - Mitch
- Stephen Bishop - Kincaid
- Cas Anvar - Omer Jarrah
- George Alan - Male flight attendant
- Bai Ling - Achara
- Faran Tahir - Ishmael Bakir
- Graham McTavish - Sergeant
- William Sanderson - Oldham
- DJ Qualls - Johnny
- Patricia Hastie - Nurse
- Jeannetta Arnette - Lizzy Calloway
- Alice Evans - Eloise Hawking
- Larry Joshua - LAX Customs Official
- Eric Lange - Stuart Radzinsky
- Mary Mara - Jill
- Patrick J. Adams - Peter Talbot
- Brad William Henke - Bram
- Kevin Durand - Martin Keamy
- Chard Hayward - Australian Official
- Robin Weigert - Rachel Carlson
- Colby French - Uncle Doug
- Stephen Semel - Adam
- Cleo King - Tamara Fry
- Rob McElhenney - Aldo
- Sterling Beaumon - Young Benjamin Linus
- Sean Whalen - Neil 'Frogurt'
- Tracy Middendorf - Bonnie
- M.C. Gainey - Tom Friendly
- Marc Vann - Ray
- Phil Abrams - Mr. Gellert
- Mark Pellegrino - Jacob
- Carrie Preston - Emily Linus
- Zoë Bell - Regina
- John Hawkes - Lennon
- Hiroyuki Sanada - Dogen
- Madeline Carroll - Annie
- Sonya Walger - Penelope Hume
- Galyn Görg - Nurse
- Michelle Forbes - Karen Decker
- Samantha Mathis - Olivia
- Titus Welliver - Man in Black
- Todd Bryant - Mattingly
- Susan Duerden - Carole Littleton
- Marc Menard - Montand
- Theo Rossi - Sgt. Buccelli
- Jeanna Garcia - Shawna
- Arlene Newman - Carole Littleton
- George O'Hanlon Jr. - Eddie
- Devon Gearhart - Young Ethan
- Aramis Knight - Sam
- Glenn Cannon - Priest
- Holland Roden - Emily
- Steven Neumeier - Lewis
- Jenny Chang - Rachel
- Marsha Thomason - Naomi Dorrit
- Sam Anderson - Bernard Nadler
- L. Scott Caldwell - Rose Nadler
- Tania Raymonde - Alex Rousseau
- Andrea Gabriel - Nadia Jaseem
- Billy Ray Gallion - Randy
- Kanayo Chiemelu - African Man
- Matt Moore - Husband
- John O'Hara - Jack Shephard
- Mira Furlan - Danielle Rousseau
- Andy Trask - Hotel Manager
- Billy Mayo - Kilo
- Kimberly Stahl - Wife
- John Terry - Christian Shephard
- Navid Negahban - Omar
- Tim Halligan - Hutton
- Necar Zadegan - Translator
- Victor Browne - Shooter
- Christian Bowman - Steve Jenkins
- Adam Leadbeater - Malcolm
- Josiah D. Lee - Tai Soo
- Allison Janney - Mother
- Kelly Rice - Nicole
- David Starzyk - Brian Porter
- Natasha Goss - Dagne
- Darren Richardson - Tommy
- Susse Budde - Mary Ford
- Byron Chung - Woo-Jung Paik
- Joey Yu - Byung Han
- Jayne Taini - Martha Toomey
- Ron Marasco - Ken Halperin
- Dann Seki - Dr. Curtis
- David Ross Paterson - Agent Hewitt
- Kimberley Joseph - Cindy Chandler
- Dylan Minnette - David Shephard
- Sheila Kelley - Zoe
- Christopher Amitrano - Burditt
- Fisher Stevens - George Minkowski
- Lance Reddick - Matthew Abaddon
- Teresa Huang - Surgeon
- Daniel Roebuck - Leslie Arzt
- Michael Cudlitz - Mike Walton
- Jonathan Dixon - JD
- Suzanne Turner - Ticket Agent
- Kevin E. West - Detective Calderwood
- Terasa Livingstone - Lily
- Wendy Braun - Gina
- Michelle Arthur - Michelle
- Blake Bashoff - Karl Martin
- Lillian Hurst - Carmen Reyes
- Bruce Davison - Douglas Brooks
- Steve Boatright - Mike
- Steve Boatright - Officer
- Steve Boatright - Goon
- Fionnula Flanagan - Eloise Hawking
- François Chau - Pierre Chang
- Samm Levine - Clerk
- Greg Grunberg - Seth Norris
- Kayren Butler - Doctor
- Christopher McGahan - Techie
- Sundra Oakley - Lawyer
- Natalie Garcia Fryman - Ms. Kendall
- Juan Carlos Cantu - Father Suárez
- Davo Coria - Servant
- Izzy Diaz - Ignacio
- Jose Yenque - Doctor
- Peter Stray - Doctor
- Alan Seabock - Sub Commander
- Alan Seabock - Sub Captain
- Lela Loren - Claudia
- Kim Kim - Mrs. Shin
- Melinda Hsu Taylor
- Jean Higgins
- Pat Churchill
- Ra’uf Glasgow
- Sarah Caplan
- Richard Peter Schroer
Rick Overton interpreta a Matthew Reed en la serie.
Allison Janney hace el papel de Mother.
Jeannetta Arnette hace el papel de Lizzy Calloway.
Hakeem Kae-Kazim interpreta a Emeka en la serie.
Jeremy Davies interpreta a Daniel Faraday en la serie.
Dominic Monaghan hace el papel de Charlie Pace.
William Sanderson interpreta a Oldham en la serie.
Bill Duke interpreta a Warden Harris en la serie.
Kevin Chapman interpreta a Mitch en la serie.
Saul Rubinek hace el papel de Clark Finney.
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