Acute liver failure (ALF) is a rare but highly morbid condition that is optimally managed by a multidisciplinary team of surgeons, hepatologists, and intensivists at a tertiary care center that specializes in liver disorders. ALF is caused by four primary mechanisms, including viral infections (most commonly Hepatitis A and B); toxicity from acetaminophen overdose or other substances; postoperative hepatic failure ; and miscellaneous causes such as autoimmune hepatitis, genetic disorders, or idiopathic etiologies. Unlike chronic liver failure in which the body develops compensatory, protective mechanisms, ALF may be associated with severe multisystem organ involvement, including respiratory distress syndrome, renal failure, and cerebral edema. Fulminant hepatic failure represents a rapidly progressive form of ALF that portends worse prognosis. Prompt diagnosis and management of multisystem organ dysfunction in an intensive care setting is paramount to survival. However, a subset of patients will fail to improve with medical management alone. Early identification of these individuals for emergent transplant listing has been shown to improve outcomes. Multiple predictive models for ALF survival have been developed, which are based on weighted evaluation of clinical and laboratory parameters. These models may be used to facilitate treatment, predict prognosis, and guide transplant listing. In this chapter, we provide an in-depth review these concepts, focusing on the classification, epidemiology, diagnosis, and management of ALF. This review contains 5 tables and 69 references. Key Words: acute liver failure, acute respiratory distress syndrome, coagulopathy, cerebral edema, fulminant hepatic failure, hepatic necrosis, liver transplantation, metabolic disarray, multidisciplinary intensive care, prognostication