Recent reported outbreaks of Clostridium difficile-associated disease in Canada have changed the profile of C difficile infections. Historically, C difficile disease was thought of mainly as a nosocomial disease associated with broad-spectrum antibiotics, and the disease was usually not life threatening. The emergence of an epidemic strain, BI/NAP1/027, which produces a binary toxin in addition to the 2 classic C difficile toxins A and B and is resistant to some fluoroquinolones, was associated with large numbers of cases with high rates of mortality. Recently, C difficile has been reported more frequently in nonhospital-based settings, such as community-acquired cases. The C difficile disease is also being reported in populations once considered of low risk (children and young healthy women). In addition, poor response to metronidazole treatment is increasing. Faced with an increasing incidence of C difficile infections and the changing profile of patients who become infected, this paper will reexamine the current concepts on the epidemiology and treatment of C difficile-associated disease, present new hypotheses for risk factors, examine the role of spores in the transmission of C difficile, and provide recommendations that may enhance infection control practices.