This issue of Infectious Disease Clinics of North America, guest edited by Dr. Mark H. Wilcox, is devoted to Clostridium Difficile Infection. Articles in this issue include: Potential sources of C. difficile for human infection, Colonisation versus carriage of C. difficile, Diagnostic pitfalls in C. difficile infection, The epidemiology of C. difficile infection in and outside of healthcare institutions, What makes epidemic C. difficile strains epidemic?: Fact versus fiction, Environmental interventions to control C. difficile infection, The contribution of strains and hosts to outcomes in C. difficile infection, Treatment of C. difficile infection, Faecal microbiota transplantation for the management of C. difficile infection, The morbidity, mortality, and costs associated with C. difficile infection, The potential of probiotics to prevent C. difficile infection, The prospect for vaccines to prevent C. difficile infection, and Predictive value of models of C. difficile infection.