Clostridium difficile infection is an important health care-associated infection. The incidence and severity of C. difficile infection are increasing. Recent C. difficile infection outbreaks with high proportions of severe outcomes have been linked to an emerging, hypervirulent strain of C. difficile. Recently recognized risk factors of C. difficile infection include fluoroquinolone exposure and gastric acid suppression. Effective prevention measures for C. difficile infection include contact precautions and antimicrobial stewardship. Awareness of C. difficile infection is critical to provide appropriate clinical care.