Clostridium difficile is emerging as a common cause of infectious diarrhea. Incidence has increased dramatically since 2000, associated with a new strain that features both increased toxin production and increased resistance to antibiotics. For patients with mild to moderate disease, oral metronidazole is usually the first choice of treatment, and those with severe disease should be treated with vancomycin, with additional intravenous metronidazole in some cases. Fecal microbiota transplantation is a potentially promising therapy for patients with multiple recurrences of C difficile infection. Prevention of nosocomial transmission is crucial to reducing disease outbreaks in health care settings.