Acute severe ulcerative colitis is a serious condition that requires early hospitalization, with intensive monitoring and treatment. Despite the recent progress in the medical approach of Inflammatory Bowel Diseases acute severe ulcerative colitis remains a clinical challenge, with a mortality rate of nearly 1%. As of today, I.V. corticosteroids remain the 1(st)-line therapy for this complication. For non-responders (up to one-third of patients) possible options are surgery - whose timing is a critical point in the overall management of the disease - or rescue therapy with 2(nd)- line agents such as Cyclosporine and Infliximab. Here we will review the published studies dealing with the use of these medications in acute severe ulcerative colitis.