Acute liver failure (ALF) is a widespread problem with typically unfavorable prognosis. With the implementation of a liver support device in the clinical setting for treatment of patients with ALF, anticipated improvements include prolonging time available for spontaneous recovery and bridging to liver transplantation. Liver support could also serve to prevent systemic manifestations of ALF such as renal failure, pulmonary edema, systemic inflammatory response syndrome and cerebral edema evolving to brain death. Both non-cell based and cell based (bio-artificial) systems have been used in clinical trials. Systems with closed or open loop organization present different advantages and disadvantages; systems also differ in the membrane pore size for filtrate/dialysate exchange. Further optimization of liver assist devices is still required; when a system has proved to be successful in treating the debilitating results of ALF, the benefits will be enormous to liver failure patients.