The epidemiology of Clostridium difficile infection (CDI) is changing. CDI, usually depicted as a nosocomial infection in the elderly, is now occurring in community-dwelling persons who are younger and otherwise dissimilar. A more virulent isolate (North American Pulsed Field type 1 (NAP1) associated with increased morbidity and mortality, has been identified. In 2005, similar strains were associated with severe disease in community-dwelling patients at a rate of 7.6/100,000. Screening patients with potential CDI symptoms and implementing preventative measures, including judicious use of antibiotics, can reduce disease burden.