Acute liver failure (ALF) in children differs from that observed in adults in both the etiologic spectrum and the clinical picture. Children, particularly very young ones, do not demonstrate classical features of encephalopathy and the definition of ALF has been revised to include patients with advanced coagulopathy, regardless of mental status. A significant number of these children will go on to require transplant or die. Etiologies vary by age with metabolic and infectious diseases prominent in the first year of life and acetaminophen overdose and Wilson's disease occurring in adolescents. In almost 50% of cases, however, the child has an indeterminate cause for ALF. Management requires a multidisciplinary approach and is directed at establishing the etiology where possible and monitoring, anticipating, and managing the multisystem complications that occur in children with ALF. Overall, short-term outcomes are better in children than adults but are dependent upon the degree of encephalopathy and diagnosis.