Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases.