We have proposed a combined osmolar-hemodynamic disturbance to explain the presence of brain edema in fulminant hepatic failure, a major cause of death in this disorder. The concept of an osmotic disturbance in the brain, emphasizing the presence of astrocyte swelling and low-grade cerebral edema, has been expanded to the entire spectrum of liver disease. The mechanism of cerebral hyperemia in patients with FHF and brain swelling has been studied in experimental models linking hyperammonemia and glutamine generation in astrocytes to the development of this hemodynamic alteration. Measures to control cerebral hyperemia, such as mild hypothermia, are effective in preventing the development of brain edema in experimental models as well as intracranial hypertension in human disease.