Pediatric acute liver failure is a rare process that results from many different diseases including toxin ingestion and drug overdose, infections, metabolic and genetic disorders, immune-mediated diseases, and ischemia. Up to 50% of children with acute liver failure will never have an underlying cause found. Early identification, supportive care, and disease-directed therapy are critical. For some children liver transplantation is needed for survival, but many children will recover with appropriate therapy, without the need for transplantation. Nonetheless, overall survival is approximately 50% without liver transplantation. Opportunities for improvement in the care of children with acute liver failure still exist.