Clostridium difficile is an important gastrointestinal pathogen in humans and animals. Disease occurs after intestinal colonization with toxigenic strains of C. difficile and subsequent proliferation due to disturbances of the microbiota. Several animal species can be affected, but mainly pigs and horses, and occasionally dogs, develop clinical disease. Pathogenesis appears to be similar in animals and humans. Initially, this disease was mainly considered to be a nosocomial infection after antimicrobial exposure; now, it often has a community onset without prior antimicrobial exposure. Therefore, reservoirs of C. difficile including animal feces, food, and the environment have recently been investigated. The bacterium has been isolated from the feces of healthy individuals from several species, including domestic and wild animals. Molecular types isolated from animals correlate with human ones, suggesting that animals could serve as an important reservoir. The use of antimicrobials appears associated with infection patterns and resistance profiles of C. difficile.