Severe hepatitis A infection is an infrequent but well-recognized cause of acute liver failure that can now be effectively prevented with vaccination against hepatitis A virus. Bromfenac and troglitazone hepatotoxicity as well as various herbal remedies are some of the newly identified causes of acute liver failure. The recently identified transfusion-transmitted virus has been implicated in some cases of idiopathic acute liver failure whereas hepatitis G virus does not appear to be a causative agent. Recognizing, monitoring, and treating patients with life-threatening cerebral edema remain critically important but difficult aspects of the clinical care of acute liver failure. Hypothermia and N-acetylcysteine are promising experimental approaches to cerebral edema but emergency liver transplantation is the only proven means of improving patient survival. Although recent changes in organ allocation may reduce waiting time to transplantation, more reliable and validated markers of liver regeneration and prognosis are needed to triage patients. The potential application and limitations of novel technologies including bioartificial liver devices and auxiliary liver transplantation continue to evolve from pioneering work in animal models and human subjects.