Liver failure results in significant alterations of the brain glutamate system. Ammonia and the astrocyte play major roles in such alterations, which affect several components of the brain glutamate system, namely its synthesis, intercellular transport (uptake and release), and function. In addition to the neurological symptoms of hepatic encephalopathy, modified glutamatergic regulation may contribute to other cerebral complications of liver failure, such as brain edema, intracranial hypertension and changes in cerebral blood flow. A better understanding of the cause and precise nature of the alterations of the brain glutamate system in liver failure could lead to new therapeutic avenues for the cerebral complications of liver disease.