Without adequate liver function, the body is unable to sustain several vital metabolic functions, such as energy supply, acid-base balance and thermoregulation. Whereas the clinical picture of chronic liver failure is often dominated by portal hypertension, fulminant hepatic failure (FHF) is typically characterized by an acute metabolic deficit. Another important distinction between these two conditions is that the liver can recover from an acute injury such as FHF. Hepatocytes retain the ability to divide in vivo; therefore, recovery from FHF is possible, although rare, if the liver can regenerate before the patient succumbs to the disease. This review examines the theoretical and practical aspects of metabolic liver support, with FHF as the paradigm.