Clostridium difficile has recently become recognized as an important nosocomial pathogen. This review summarizes what is known about the isolation of the organism, the spectrum of clinical disease, virulence factors, treatments, and methods of prevention. Risk factors for C. difficile disease are also discussed. The most important risk factor is the use of certain antibiotics (ampicillin, cephalosporins, and clindamycin). C. difficile is associated with 96% to 100% of cases of pseudomembraneous colitis, 60% to 75% of antibiotic-associated cases of colitis, and 11% to 33% of antibiotic-associated cases of diarrhea. Other risk factors include gastrointestinal manipulations, advanced age, female sex, inflammatory bowel disease, cancer chemotherapy, and renal disorders. Hospital outbreaks of C. difficile disease are examined. Data from nosocomial outbreaks support transmission of C. difficile by contaminated fomites and hand carriage by hospital personnel.