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.