In the last few years, several abnormalities of cerebral blood flow (CBF), namely loss of cerebral autoregulation, altered reactivity to carbon dioxide, and development of cerebral hyperemia, have been described in patients as well as experimental models of acute liver failure (ALF) and/or hyperammonemia. The development of cerebral hyperemia seems particularly relevant to the pathogenesis of brain edema in ALF. In addition to the potential increase of brain blood volume causing a rise in intracranial pressure, an increase of CBF could facilitate the movement of water across the blood brain barrier in an osmotically altered brain. Because maneuvers that abrogate the rise of CBF have been shown to prevent or ameliorate brain edema in ALF/hyperammonemia, elucidation of the mechanism by which the rise of CBF occurs is important. In the rat after portacaval anastomosis receiving an ammonia infusion, the signal resulting in cerebral hyperemia arises within the brain once maximal glutamine accumulation has occurred in astrocytes. Several mediators potentially involved in the development of cerebral hyperemia in ALF are examined in this review, but further work is needed to assess the role, if any, of each of them.