Acute severe ulcerative colitis is a potentially lethal condition that requires a pro-active approach with either effective medical treatment or timely colectomy. Although intravenous corticosteroids remain the first line treatment, in patients not responding after 3-5 days rescue medical therapy with either intravenous (IV) cyclosporine 2 mg/kg or infliximab 5 mg/kg IV should be considered. Controlled evidence supports the use of both treatments but medical rescue therapy should not defer the decision for colectomy in patients with inadequate response. Providing clear guidance for the choice between both agents is impossible due to the lack of comparative trials. The better short-term safety profile and the option for maintenance treatment favour infliximab specifically in patients already exposed to immunosuppressives. The rapid onset of action and the short half-life are advantages of cyclosporine in patients with imminent risk of colectomy. Even if cyclosporine and probably also infliximab only postpone colectomy in at least half of the patients, elective colectomy in a later stage of the disease may offer better outcomes. Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase perioperative morbidity in ulcerative colitis.