Acute liver failure is a rare but often catastrophic illness affecting the liver and multiple organ systems. Patients with acute liver failure require a multidisciplinary approach for adequate management. With improved critical care and the availability of liver transplantation, survival has significantly improved. Hepatic encephalopathy, cerebral edema and infections are the most common complications of acute liver failure. The evaluation requires a diligent search for a specific etiology of the liver failure, since certain causes may respond well to specific pharmacological therapies. Acetaminophen and non-acetaminophen drug-induced hepatotoxicity account for more than 50% of cases of acute liver failure. Assessment of prognosis frequently (at least on a daily basis) by using various prognostic tools, allows the treating team to decide whether or not to proceed with urgent liver transplantation. Artificial liver support devices are still in evaluation and not ready for use in clinical practice. While it is determined whether or not there is sufficient hepatic regeneration, the care of the patient with acute liver failure revolves around managing the dysfunction of multiple extra hepatic systems.