Orthotopic liver transplantation is employed as salvage therapy for individuals who are unable to recover from acute liver failure. Prognostic models are helpful but not entirely accurate in predicting those who will eventually require liver transplantation. There are specific criteria for United Network for Organ Sharing category 1a (urgent) listing of these patients. Unfortunately, clinical deterioration develops rapidly and many require removal from the waiting list prior to transplantation. With advances in critical care management and surgical technique, 1-year post-transplant survival rates have improved to 60 to 80%. Alternatives to conventional orthotopic liver transplantation include living donor liver transplantation, ABO-incompatible grafts, and auxiliary liver transplantation. There are many ethical and psychosocial issues inherent to transplanting these sick patients due to the urgent nature of acute liver failure. Fortunately, the long-term survival and quality of life in these transplant recipients is good.