FHF is an uncommon but devastating condition affecting otherwise healthy persons which causes significant morbidity and mortality. The etiologic factor is most commonly viral infection, with drugs and metabolic disorders being relatively less common causes. Hopefully, newer diagnostic techniques such as PCR will increase our understanding of the causes and pathogenesis of this disorder. Medical management at the present time must focus on anticipating, preventing, and rapidly identifying and treating complications that may affect every major organ system. Encouraging research continues on the clinical application of hepatotrophic drugs and artificial liver support systems, both as potentially definitive therapies and as maintenance for patients awaiting transplantation. Consultation with physicians at a transplant center should be sought early in the course of the patient's hospitalization when OLT is being considered. Liver transplantation has dramatically changed the outlook for patients with FHF, with current survival rates in the 55% to 75% range. The continuing challenge for the transplant team is to allocate available donor organs to those patients who would not otherwise survive, but also to provide OLT in a timely fashion to ensure the best chance of post-transplantation recovery. Newer techniques such as heterotopic liver transplantation, reduced-size organ transplantation, and the utilization of living related donors may further improve the survival of these patients.