The understanding and treatment of acute hepatic failure has developed rapidly over the last 40 years reducing morbidity and mortality from this syndrome. Progress has been made by the study of animal models that reflect the clinical, biochemical and histological pattern of the syndrome seen in man. This is of increasing importance with the use of therapeutic intervention, liver transplantation and the use of extra-corporeal liver support devices. This review examines and critically appraises the various approaches to the study of acute hepatic failure in animal models, including both surgical and pharmacological approaches.