Clostridium difficile associated disease (CDAD) is the cause of significant and increasing mortality and morbidity in Australia and worldwide. Though traditionally thought of as a hospital associated disease, growing evidence suggests that community acquired CDAD is at least as common and may be the source of many hospital cases. Understanding CDAD requires considering the effects of the interaction of C. difficile, its toxins, the human immune system, gut flora and antibiotics. Mathematical modelling of all these factors can be used to confirm, support or generate new hypotheses regarding the difference in epidemiology between the hospital and community, the causes of seasonal patterns, the relative importance of different forms of transmission, and optimum clinical interventions to reduce transmission and recurrence.