Acute liver failure is a life-threatening illness precipitated by an acute liver injury in patients with no pre-existing liver disease. Acute viral hepatitis and drug-induced liver injury account for most cases, the clinical course characterized by the development of coagulopathy and hepatic encephalopathy, often progressing to multi-organ disease, which is associated with high fatality rates. The outcomes have improved significantly over time with improving standards of organ system support and access to liver transplantation for very sick individuals.