Patients with acute liver failure are critically ill and their survival depends not only on the capacity of the liver to regenerate but also on intensive supportive medical management. There is no effective therapy for any of the major known causes of acute liver failure. Most cases of non-A, non-B hepatitis-related acute liver failure are also non-C, non-E hepatitis-related. The role of the newly described hepatitis viruses in the etiology of acute liver failure is unknown. Cerebral edema is a common complication of acute liver failure, and its pathophysiology and treatment have been recently explored. Selection of patients likely to survive is important in order to determine which patients require liver transplantation. Increased effort has been placed in developing prognostic factors or criteria that predict a need for liver transplantation. Due to the shortage of donor organs, alternatives to orthotopic liver transplantations continue to be explored.