Intravenous steroids are considered the mainstay of treatment in patients with severe ulcerative colitis. Several randomized controlled trials have been designed to evaluate drugs that, as an adjunct to intravenous steroids, could obtain a clinical response and avoid colectomy in patients who do not respond to corticosteroids. For steroid refractory patients, cyclosporine and infliximab seem to be an effective alternative to colectomy in the short term, but more data are needed to evaluate if they can prevent colectomy also in the long term. Although there is no evidence from the published trials that antibiotics as adjunctive therapy may have an additional benefit, therapeutic protocols for severe ulcerative colitis generally include antibiotics for patients with signs of toxicity, or with worsening of symptoms despite the medical treatment. No additional benefit over steroids has been shown from bowel rest. Moreover, as bowel rest deprives the colonic enterocytes of the short-chain fatty acids vital to their metabolism and repair, it may even be harmful. Conflicting results have been published on heparin as primary treatment of severe ulcerative colitis; at the present time there is no evidence supporting its use. Although "steroid-free" clinical remission is, at this time, the most important end point of clinical studies in inflammatory bowel disease, only few data are available in steroid dependent colitis patients. Azathioprine seems to be effective in inducing steroid-free remission.