Clostridium difficile, a pathogen first described in the late 1970s, has become a leading cause of hospital-associated diarrhea in humans and a leading cause of enteritis in neonatal piglets. As a spore-forming bacteria, C. difficile reproduces easily in the colon with a low gut microflora. Spores are located in dirt, other species, water, and other environmental surfaces. Toxins that are known to play a role in Clostridium difficile Infections (CDI) are Toxin A and Toxin B. The third toxin, binary toxin, is still unknown regarding its role in CDI. These toxins can produce symptoms such as diarrhea, toxic megacolon, enteritis, lesions on the intestines, and in extreme cases death. Since the discovery, different species models have been researched for more effective therapies in humans. This review shows how humans and other species can benefit by researching Clostridium difficile in pig models.