Clostridium difficile is a major cause of antibiotic-associated diarrhea. While treatment regimens for C. difficile have been available for decades, they remain less than optimal due to the frequent recurrences that occur after therapy is completed. Moreover, the morbidity and expense associated with C. difficile have underscored the need for more effective preventive measures than are currently available. In this review, we outline the current recommendations for treatment and prevention of C. difficile infection and, highlight some promising new approaches that may help to control this common nosocomial pathogen in the future.