Worldwide, viral infection is responsible for the majority of cases of acute liver failure, and the presence of co-existing chronic viral hepatitis may increase its severity. The newly described hepatotrophic viruses, hepatitis G virus and transfusion-transmitted virus, are unlikely to be major aetiological agents. In the USA and western Europe drug-induced hepatotoxicity is the most common cause, and most frequently results from acetaminophen. Hepatotoxicity caused by Ecstasy is increasingly important, particularly in young adults. Hepatic encephalopathy and cerebral oedema remain important and life-threatening complications, and their pathogenesis is not completely understood. The effects of the cerebral metabolism of the high levels of ammonia that circulate in hepatic failure appear to be important. Induced hypothermia is a promising modality of treatment for refractory cerebral oedema, but the only form of treatment known to improve survival is emergency liver transplantation. Living donor and auxiliary liver transplantation are likely to improve survival rates further and reduce the number of patients requiring long-term post-transplant immunosuppression.