The anaerobic spore-forming bacillus, Clostridium difficile (C difficile), has emerged as a serious infection over the past decade, more than doubling in incidence in North American medical centers. Clostridium difficile-associated disease (CDAD), which can range from mild watery diarrhea to pseudomembranous fulminant colitis with toxic dilation and perforation, affects >500 000 persons in the US annually and is linked to the death of >15 000 of these individuals. Studies from referral centers as well as administrative databases have shown that patients with IBD (Crohn's disease or ulcerative colitis), specifically those with underlying colitis, are at an increased risk for C difficile carriage as well as for contracting CDAD. More importantly, there is overlap in clinical presentation of the infection and IBD, and CDAD can mimic a flare of IBD colitis. The detection of the superinfection, with rapid implementation of appropriate antibiotic agents against C difficile, is essential to improve clinical outcome. IBD patients infected with C difficile are at an increased risk for hospitalization, colectomy, and mortality compared with uninfected counterparts. CDAD is also associated with unique clinical scenarios in IBD, specifically causing infection in ileo-anal pouches and ileostomies. Toxin enzyme-linked immunosorbent assays (ELISA) may be less sensitive in IBD patients than in those without IBD, requiring multiple samples to confirm the diagnosis. Oral vancomycin may function as the optimal treatment for hospitalized IBD patients with CDAD. Concomitant immunosuppression may predispose to more serious infection, and new data suggest that corticosteroid use correlates with infection. Repeat infection may occur in a substantial number of patients, and prior antibiotic exposure may not be identified in a subgroup of IBD patients with CDAD. Awareness of the rise in C difficile infections, and identification of this confounding issue with rapid initiation of appropriate treatment is essential to achieve optimal IBD patient outcomes. [ABSTRACT FROM AUTHOR]