Clostridium difficile colitis has doubled in North America over the past 5 years and recent reports have demonstrated an increase in incidence and severity of these infections in patients with inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis). Studies from single institutions as well as trends identified in nationwide inpatient databases have shown that IBD patients with concomitant C. difficile infection experience increased morbidity and mortality. Results from our center have shown that over half of C. difficile-infected IBD patients will require hospitalization and the colectomy rate may approach 20%. Because C. difficile colitis will both mimic and precipitate an IBD flare, it is essential that clinicians be vigilant to identify and address this infectious complication, as empiric treatment with corticosteroids without appropriate antibiotics may precipitate deterioration. The majority of IBD patients appear to contract C. difficile as outpatients, and a prior history of colitis appears to be the most significant risk factor for acquiring this infection. In addition to C. difficile colitis, IBD patients are now known to be at risk for C. difficile enteritis as well as infections in reconstructed ileoanal pouches. An additional challenge facing C. difficile infections in IBD patients is the decreased efficacy of metronidazole, and the need for oral vancomycin in patients requiring hospitalization. In this review we summarize the present knowledge regarding C. difficile infection in the setting of IBD, including unique clinical scenarios facing IBD patients, diagnostic algorithms, and treatment approaches.