Vo filme Kniha života hrajú Diego Luna (Manolo (voice)), Channing Tatum (Joaquin (voice)), Zoe Saldaña (Maria (voice)), Christina Applegate (Mary Beth (voice)), Eugenio Derbez (Chato (voice)), Cheech Marin (Pancho Rodriguez (voice)), Gabriel Iglesias (Pepe Rodriguez (voice)), Ron Perlman (Xibalba (voice)), Kate del Castillo (La Muerte (voice)), Ana de la Reguera (Carmen Sánchez (voice)), Dan Navarro (Chakal (voice)), Ice Cube (Candle Maker (voice)), Hector Elizondo (Carlos Sanchez (voice)), Danny Trejo (Skeleton Luis (voice)), Carlos Alazraqui (General Posada / Dali / Chuy (voice)), Emil-Bastien Bouffard (Young Manolo (voice)), Elijah Rodriguez (Young Joaquin), Genesis Ochoa (Young Maria (voice)), Plácido Domingo (Skeleton Jorge (voice)), Grey DeLisle (Grandmother (voice) (as Grey Griffin)), Trey Bumpass (Goth Kid / Orphan), Miguel Sandoval (Land of the Remembered Captain (voice)), Ben Gleib (Goya / Dali (voice)), Ricardo El Mandril Sanchez (Pablo Rodriguez (voice)), Ishan Sharma (Sanjay), Jorge R. Gutierrez (Skeleton Carmelo (voice)), Anjelah Johnson-Reyes (Adelita / Nina (voice)), Kennedy Peil (Sasha (voice)), Sandra Equihua (Scardelita (voice)), Callahan Clark (Jane (voice)), Gunnar Sizemore (Ignacio (voice)), Angélica María (Sister Ana (voice)), Eric Bauza (Father Domingo / Cave Guardian (voice)), Aron Warner (Thomas (voice)), Sandra Echeverría (Claudia (voice)), Tonita Castro (La Muerte as Old Woman (voice)), Troy Evans (Old Man Hemingway (voice)), Guillermo del Toro (Land of the Remembered Captain's Wife (voice)), Brad Booker (Conductor (voice)), Rosemary Alexander (Additional Voices (voice)), Steve Alterman (Additional Voices (voice)), Eva Bella (Additional Voices (voice)), Madison Carlon (Additional Voices (voice)), Vicki Davis (Additional Voices (voice)), Moosie Drier (Additional Voices (voice)), Cullen McCarthy (Additional Voices (voice)), David Michie (Additional Voices (voice)), Michelle Moores (Additional Voices (voice)), Jonathan Nichols (Additional Voices (voice)), Al Rodrigo (Additional Voices (voice)), Marcelo Tubert (Additional Voices (voice)), Lynnanne Zager (Additional Voices (voice)), Ruth Zalduondo (Additional Voices (voice)), Newell Alexander (Additional Voices (voice)), David Cowgill (Additional Voices (voice)), Elisa Gabrielli (Additional Voices (voice)), Richard Miro (Additional Voices (voice)), Arthur Ortiz (Additional Voices (voice)), Nathaniel Semsen (Additional Voices (voice)), Joe Matthews (Young Manolo (singer)), Jose Alvarez (Additional Voices (voice) (uncredited)).