Clostridium difficile associated disease (CDAD) is the result of colonic bacterial overgrowth with this gram positive anaerobic organism and the production of toxins that typically induce diarrhea. Most patients with CDAD respond to treatment with oral metronidazole or vancomycin, but a subset of patients will develop a severe systemic illness, multiple organ failure, and death. There are no reliable combinations of clinical or laboratory findings that will distinguish patients who will respond to medical therapy and those who will progress to a more complicated state. Early surgical consultation should be considered in patients with ileus, severe abdominal pain, significant tenderness, immunosuppression, advanced age, high white blood cell or band counts, acute renal failure, mental status changes, or cardiopulmonary compromise. The standard operation for fulminant colitis is subtotal colectomy but the high mortality of the operation, and the long-term morbidity even in survivors combine to act as deterrents to early surgical consultation and operation. Novel operative approaches that preserve the colon and minimize operative morbidity may prove to remove the barriers to earlier surgical treatment for fulminant CDAD and improve outcomes.