Acute liver failure (ALF) is a life-threatening disorder characterised by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease. The cause of ALF varies across the world. Common causes of ALF in adults include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis. The cause of liver failure affects the management and prognosis, and therefore extensive investigation for cause is strongly suggested. Sepsis with multiorgan failure and cerebral oedema remain the leading causes of death in patients with ALF and early identification and appropriate management can alter the course of ALF. Liver transplantation is the best current therapy, although the role of artificial liver support systems, particularly therapeutic plasma exchange, can be useful for patients with ALF, especially in non-transplant centres. In this Seminar, we discuss the cause, prognostic models, and management of ALF.