Corticosteroids are the mainstay of therapy for severe ulcerative colitis. However, at least a third of patients fail to respond and face a colectomy. In these, rescue therapy with cyclosporine or infliximab (IFX), aimed at avoiding surgery, has been used in recent years. Of the two options, infliximab is largely preferred in both Sweden and Norway, whereas cyclosporine (CyA) is generally regarded as difficult to use, rather toxic and showing limited long-term efficacy. In light of some new recent data, herein, we provide an update of the literature in the field. It appears that there are theoretical and practical arguments on each side, and as of today, the choice between IFX or CyA for rescue therapy cannot be made on strong evidence. Thus, the best choice of medical rescue therapy will depend on the results of ongoing RCTs as well as future research in the field.