- Oscar de la Hoya - Tony
- Bryan Fisher - Jason McNamara
- Lou Diamond Phillips - George L.
- Ashley Tisdale - Olivia
- Andy García - Ray
- Eva Longoria - Brooke
- Ken Howard - Dr. Woodson
- Freddie Prinze Jr. - Freddie Moreno
- Ming-Na Wen - Professor Lim
- Jason Stuart - Sales Managerr
- Richard Riehle - Eddie Carter
- William Hung - William Hung
- Paget Brewster - Ginger
- Rita Moreno - Luisa Diaz
- Mario López - Officer Hector Sanchez
- Jason Connery - Mike
- Peter MacKenzie - Dr. Loftusi
- Mayan Lopez - Jackie
- Elena Lyons - Mary
- Kristin Bauer - Chris Watson
- Edward James Olmos - Mr. Vega
- Ismael 'East' Carlo - Uncle Joe
- Cheech Marin - Lalo
- Jacqueline Obradors - Gloria
- Nick Offerman - Randy
- Marilyn Milian - Judge Alvarez
- Trevor Wright - Zack Powers
- Cristina Saralegui - Lydia
- Ron Pearson - Officer Robinson
- Chloe Bridges - Zoey
- Maria Canals-Barrera - Claudia
- Sônia Braga - Emilina Palmero
- Tommy Chong - Mr. Gutierrez
- Robert Rodriguez - Robert Rodriguez
- Donovan McNabb - Donovan McNabb
- Esai Morales - Manny Lopez
- James Lesure - Ben Adams
- John Michael Higgins - Charles
- Dagney Kerr - Claudia
- Adam West - Jonathan K. Martin
- Sandra Bullock - Amy
- Jack Blessing - Jack Powers
- Brian Austin Green - Chris
- Tony O'Dell - Delivery Guy
- Connie Ramirez - Aunt Lynette
- Cesar Rosas - Ceasar Rosas
- Dot-Marie Jones - The Inmate
- Jerry Springer - Wayne
- Hilary Duff - Stephanie
- Stacy Keibler - Lindsay
- Elmarie Wendel - Gina
- Eva LaRue - Linda Lorenzo
- Bob Koherr - Carl
- Jacob Richardson - Ben
- Sam Saletta - Luke
- Mel Rodriguez - Frank
- Gregg Daniel - Jim
- Don Tiffany - Parent #1
- Jordan Calloway - Kid #2
- Hayden Tank - Kid #3
- Rory Thost - Timmy
- Klee Bragger - Kevin
- Jodi Lyn O'Keefe - Campbell
- Lillian Hurst - Mrs. Cardenas
- Jim O'Heir - Pete
- Jim O'Heir - Reggie
- Olga Merediz - Aunt Cecilia
- Clement Blake - Homeless Guy
- Mark Tymchyshyn - Mel Powers
- Autumn Reeser - Piper
- Rachel Snow - Toby
- Brenda Song - Jennifer
- Carl Anthony Payne II - Curtis
- Carly Schroeder - Ashley
- Nancy Linehan Charles - Mrs. Wilder
- Jessica Friedman - Valerie
- Kelsey Kemper - Trick or Treater
- Paige Hurd - Little Girl
- Steve Garvey - Self
- Joe Morgan - Self
- Jim Palmer - Self
- Scott Klace - Bobby Murphy
- Connie Ray - Debbie
- Jordan Masterson - Adam
- Bari Hochwald - Cindy
- Dani Goldman - Michelle
- Sarah Bibb - Meter Lady
- Tonantzin Esparza - Marisol
- Cristos - Giggles
- Diane Sellers - Emma
- Daniel Cage Theodore - Thug (uncredited)
- Emiliano Díez - Vic Palmero
- Marcelo Tubert - Señor Scrooge
- Oleg Zatsepin - Roberto Cratchett
- Sonia Iris Lozada - Narrator
- Alejandro Furth - Carlos
- Izzy Diaz - Hector
- John Balma - Construction Worker
- Steve Schirripa - Tony
- Todd Duffey - Teenage Boy (voice) (uncredited)
- Miriam Flynn - Brenda
- Kate Orsini - Bartender
- Jason Antoon - Hosni
- Branden Williams - Junior
- Casey Sander - Mr. Dugan
- Mary K. DeVault - Woman #1
- Susan Slome - Woman #2
- Josip Kuchan - Yuri
- Sara Van Horn - Jean
- William Marquez - Manny Lopez
- Amaury Nolasco - Young Manny
- Maria Beck - Young Benny
- Nicole Stuart - Rachel
- Rod Britt - Doctor
- Gerry Bednob - Mr. Gidwani
- Eloy Casados - Dr. Anthony Tovar
- Geoffrey Wade - The Doctor
- Tanika Brown McKelvy - Bailiff
- Carrie Ann Nagy - Waitress
- Zachary James Bernard - Danny
- Frank Crim - Allen
- Roger V. Burton - Walter
- Jacquie Barnbrook - Helen
- Marilyn O'Connor - Dorothy
- Hira Ambrosino - Prosecutor
- Frederick Martin Smith - Police Officer
- Joel S. Greco - Joey Greco
- Agapito Leal - Uncle Arturo
- Barbara Eden - Ruth
- Julie Wittner - Tanya
- Kincaid Walker - Nancy
- Julian Acosta - Rick Martinez
- Ashly Holloway - Kristi Chapman
- Jennifer Hasty - Dell
- Rafael Gayol - Chingon
- Kelly Mantle - Deep Voice Singer
- Zachary Morris - Mini Kiss
- Terra Jolé - Mini Kiss
- Bonnie Morgan - Rubber Girl
- Rip Taylor - Rip Taylor
- Michael Taggart - The Fireman
- Paul Anthony Reynolds - Irate Parents
- Hayden Adams - Spencer Vogel
- Erik Olson - Brad
- George Lopez
- Sandra Bullock
- Frank Pace
George Lopez hace el papel de George Lopez.
Constance Marie interpreta a Angie Lopez en la serie.
Luis Armand Garcia interpreta a Max Lopez en la serie.
Valente Rodriguez interpreta a Ernie en la serie.
Belita Moreno interpreta a Benny Lopez en la serie.
Masiela Lusha hace el papel de Carmen Lopez.
Aimee Garcia hace el papel de Veronica Palmero.
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