Clostridium difficile is the leading cause of bacterial antibiotic-associated diarrhoea in hospitals in the developed world. Despite this notoriety, the complex mechanisms employed by this pathogen to overcome innate host defences and induce fulminant disease are poorly understood. Various animal models have been used extensively for C. difficile research to study disease pathogenesis. Until recently, the most commonly used C. difficile disease model has utilised hamsters; however, mouse and pig models have now been developed that unravel different aspects of C. difficile pathology. This review summarises key aspects of the small animal models currently used in C. difficile studies with a specific focus on major differences between them. Furthermore, this review highlights the advantages and disadvantages of each model and illustrates that careful consideration is required when selecting models for use in C. difficile research.