Clostridium difficile is an important cause of nosocomial morbidity and mortality and is implicated in recent epidemics. Data support the treatment of colitis with oral metronidazole in a dose of 1.0 to 1.5 g/d, with oral vancomycin as a second-line agent, not because its efficacy is questioned but because of environmental concerns. Nitazoxanide and other drugs are currently under intense study as alternatives. Treatment of asymptomatic patients is not recommended. Current management strategies appear to be increasingly ineffective, especially for patients who experience multiple recurrences. Biotherapy and vaccination are currently being explored as treatment options for patients who have recurrent disease. Greater attention should be paid to hospital infection control policies and restriction of broad-spectrum antibiotics.