The prevalence of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) has become a focus of increased attention, as the C. difficile epidemic continues to grow. Although first documented more than 20 years ago, only in recent years has the relationship between these 2 entities been better clarified, and recent epidemiologic studies have shown that IBD patients are at increased susceptibility for CDI compared with the general population. Despite this increased attention, much still remains unknown, and the overlapping clinical presentations of CDI and IBD pose barriers to diagnosis and standardized treatment. Moreover, given the relationship between mortality and severity of CDI in IBD patients, early recognition of those who are at increased risk for infection is of paramount importance to improve patient outcome.