I t is estimated that 15% of all ulcerative colitis (UC) patients during the course of their disease have a severe attack, defined as involving digestive and systemic symptoms.1 Fulminating colitis is an even more severe attack, which identifies a subgroup of patients at risk of dying. It is characterized by any 3 of the following: fever 38°C (101.5°F), hypoalbuminemia, tachycardia ( 120 beats per minute), leukocytosis ( 10,500 mm), hemoglobin 9.6%, together with any 1 of: dehydration, mental changes, electrolyte imbalance, and hypotension.2 The systemic changes are due to inflammation that can extend beyond the submucosa, often extending to the serosa. Fulminating colitis, with or without toxic megacolon, is the main reason for emergency operative treatment of UC. Patients with fulminating colitis are extremely ill and require rapid, aggressive medical therapy, including fluid resuscitation, correction of electrolyte abnormalities, and in some cases blood transfusions. A “nihil per os” regimen is indicated. In the past the rate of mortality of this type of colitis was up to 60%, but the introduction of high-dose intravenous steroid and the policy of early surgery have reduced this figure to 1%–2%.3 The causes of death in these cases are multiple organ failure, directly correlated to bacterial translocation with septic state, and the perforation of the colon. To avoid these complications, choosing exactly the right moment to pass from medical therapy to surgical is crucial. A regimen of continuous infusion of methylprednisolone 60 mg/day, plus metronidazole and/or ciprofloxacin is the main initial medical approach. In some cases, adding 5-ASA enema is helpful. The response to this intensive regimen should be evaluated every 24 hours for 5–7 days. Cyclosporine can be used in case of unresponsiveness to steroids, but its toxicity remains a factor of concern. Some studies have recently reported a noteworthy efficacy of infliximab infusion in this severe form of colitis.4 In some centers infliximab is today the favorite option for the steroidunresponsive patient. If there is no improvement, or if the patient’s condition deteriorates, surgical treatment is recommended. UC is pathologically located in the rectum and colon, hence the possibility of a definitive surgical cure. An ileopouch–anal anastomosis permits a complete removal of the rectum and colon, but in an acute setting it is advisable to perform this surgical procedure in 3 stages. The first step is a preliminary colectomy with rectal preservation. This procedure not only reduces the high complication rate in a severely ill patient but also permits definitively excluding Crohn’s disease (CD) by examining the surgical specimen. In the case of a CD diagnosis, in fact, an ileoanal pouch has a high complication rate, and an ileorectal anastomosis can be a good alternative. An ileoanal pouch with a temporary ileostomy follows the first operation 1 or 2 months after. In conclusion, in severe toxic colitis the first commandment is to save the patient’s life; a regimen using continuous intravenous infusion of steroid plus antibiotics followed, in case of no response within 3–5 days, by cyclosporine or, preferably, in my opinion, by infliximab. Some experts object that the combination of a high dosage of steroid with a powerful immunosuppressor renders it inadvisable to add another immunosuppressor if the first regimen fails. In such a case, thanks to its rapid metabolization, the best course might be to employ cyclosporine before infliximab. In conclusion, any chosen therapeutic strategy should be continued for a maximum of 7–10 days, and in case of therapeutic failure an operation should be indicated.