Many articles have summarized the changing epidemiology of Clostridium difficile infections (CDI) in humans, but the emerging presence of C. difficile in foods and animals and possible measures to reduce human exposure to this important pathogen have been infrequently addressed. CDIs have traditionally been assumed to be restricted to health-care settings. However, recent molecular studies indicate that this is no longer the case; animals and foods might be involved in the changing epidemiology of CDIs in humans; and genome sequencing is disproving person-to-person transmission in hospitals. Although zoonotic and foodborne transmission have not been confirmed, it is evident that susceptible people can be inadvertently exposed to C. difficile from foods, animals, or their environment. Strains of epidemic clones present in humans are common in companion and food animals, raw meats, poultry products, vegetables, and ready-to-eat foods, including salads. In order to develop science-based prevention strategies, it is critical to understand how C. difficile reaches foods and humans. This review contextualizes the current understanding of CDIs in humans, animals, and foods. Based on available information, we propose a list of educational measures that could reduce the exposure of susceptible people to C. difficile. Enhanced educational efforts and behavior change targeting medical and non-medical personnel are needed.