Acute severe steroid-refractory ulcerative colitis (ASUC) provides challenges for physicians and surgeons who manage these patients. When a patient is diagnosed with ASUC, they should be admitted for inpatient management including intravenous corticosteroids, venous thromboembolism prophylaxis, oral or enteral feeding if tolerated, and exclusion of infection including Clostridium difficile. Failure to improve by day 3 of corticosteroids requires escalation to medical rescue therapies such as infliximab or cyclosporine, or surgical management with colectomy. This chapter will review management of ASUC with a focus on the medical rescue options available.