In this report the history and clinical results of heterotopic liver transplantation (HLT) are reviewed and some special aspects of current research on HLT are high-lighted. The first laboratory experiments on liver transplantation were performed with auxiliary heterotopic grafts. The initial clinical results of HLT, however, were disappointing and orthotopic liver transplantation (OLT) evolved to be the procedure of choice. Of all the patients who received a heterotopic graft before 1980, only two survived. Since 1980, 50 HLTs are known to have been performed on 48 patients. Results of HLTs after 1986 are clearly better than earlier ones, and survival rates come within the range of those reported for OLT. Intraoperative fibrinolysis is found in the anhepatic phase of OLT, something which is absent in HLT. Tissue-type plasminogen activator (t-PA) is said to be responsible for this phenomenon, as well as for the postreperfusion hyperfibrinolysis. Parallel to the hemostatic changes, the intraoperative hemodynamic stability may be impaired by deleterious substances that arise during liver transplantation. Furthermore, the interaction between the two livers, the effect of HLT on portal pressure and hypersplenism, and the possible role of HLT in inborn errors of hepatic metabolism are described. Special attention is given to the treatment of acute hepatic failure. OLT, in an early phase of the disease, negates the possibility of spontaneous recovery, while delay of the decision to transplant may lead to further deterioration of the patient's clinical condition. As the procedure of HLT is reversible, the decision to transplant can be made more quickly. The clinical experience with HLT for acute liver failure is reported in detail.