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Artificial liver support is urgently needed. Mechanical devices such as hemodialysis and hemoperfusion do not correct the metabolic abnormalities that exist in end-stage liver disease, and biologically active devices have been impracticable because of limitations in the availability and viability of cultured liver cells. This deficit in the medical armamentarium is a major concern best illustrated by current management of fulminant hepatic failure (FHF). Medical treatment for FHF is largely unsuccessful, and orthotopic liver transplantation (OLT) is the intervention against which all future therapeutic interventions must be judged. The OLT procedure, however, is not benign. The cost is high, and survivors face a lifetime of immunosuppression and medical supervision. By comparison, patients who survive without surgery recover full liver function and have a normal life expectancy. A device that provides liver support during the critical stages of FHF would stabilize patients until a suitable donor organ was found and might negate the need for transplant altogether if the liver were able to regenerate. We review theoretical and practical aspects of biologically active devices using FHF as a paradigm of liver disease.