Clostridium difficile-associated infection (CDI) can have varying severity from asymptomatic carriage to fulminant colitis. Its incidence and virulence in North America are increasing. The increase in virulence is associated with emergence of the highly toxigenic North American pulsed field gel electrophoresis-1 strain. The major risk factor for CDI is exposure to antibiotics. Another major risk factor is hospitalization. The spectrum of CDI ranges from asymptomatic carriers to fulminant disease. Although asymptomatic carriers require no treatment, fulminant disease carries a substantial mortality regardless of management strategy.