Although the incidence of Clostridium difficile–associated diarrhea in the general population has increased dramatically over the past decade, an even greater rate of infection exists in patients with inflammatory bowel disease. Susceptibility in this population is likely inherent to the pathophysiology and treatment of these diseases. C. difficile infection can cause serious complications and death. Consequently, early diagnosis and initiation of effective antibacterial therapy is imperative. This article evaluates treatment recommendations for an initial episode of C. difficile infection in patients with inflammatory bowel disease based on the current guidelines and a Cochrane systematic review.