Acute liver failure (ALF) is a clinical syndrome comprising of severe liver injury manifesting with coagulopathy and encephalopathy in the absence of preexisting liver disease. Common etiologies include acetaminophen toxicity, drug-induced liver injury, and viral hepatitis. Management of ALF is challenging with high morbidity and mortality. Recent strides in the management of ALF patients in the critical care setting and transplant availability have helped improve survival. In this chapter, we will discuss ALF, clinical manifestations, and management.