OBJECTIVE Clostridium difficile is the most common cause of nosocomial infectious diarrhea in adults. The purpose of this review is to increase awareness that infection from C. difficile is not always indolent, but with fulminant colitis, it can be lethal. The epidemiology, pathogenesis and treatment of C. difficile infection are discussed, with special emphasis on management of fulminant colitis. RESULTS Clostridium difficile causes fulminant colitis in 3-8% of patients. Early predictors of disease include immunosuppression, hypotension, hypoalbuminemia, and a pronounced leukocytosis. In patients with fulminant colitis, early colectomy before vasopressor therapy is required and may improve survival. CONCLUSIONS The incidence and virulence of C. difficile infection are increasing. Antibiotic use and length of hospital stay correlate strongly with infection. Oral or intravenous metronidazole is the recommended first-line therapy, with discontinuation of systemic antibiotics if possible. Forty percent of patients may have a prolonged course and 20% will relapse despite adequate therapy. Fulminant colitis develops in 3-8% of patients; diagnosis can be difficult with diarrhea absent in 20% of the subgroup. Once diagnosed, subtotal colectomy with ileostomy is usually required. In patients with a marked leukocytosis or bandemia, surgery is advisable because the leukocytosis frequently precedes hypotension and the requirement for vasopressor therapy, which carries a poor prognosis.