Clostridium difficile has become an increasingly important nosocomial pathogen and is one of the most common causes of hospital-acquired diarrhea. The incidence of C difficile infection (CDI) is increasing worldwide. Overuse of antibiotics is felt to be a major contributing factor leading to the increased incidence of CDI. The clinical manifestations of CDI vary from a mild form of the disease to fulminant diarrhea, leading to significant patient morbidity and mortality. The increasing incidence of CDI has a major impact on increasing health care costs. This article will summarize the epidemiology, pathogenesis, clinical manifestations, laboratory diagnosis, and treatment options for CDI, as well as infection-control measures for the prevention of CDI.