A great deal of work with animal models indicates that hepatocytes transplanted into the liver or spleen survive, function, and participate in the normal regenerative process. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to whole organ transplantation and for providing metabolic support during liver failure and for replacing whole organ transplantation in certain metabolic liver diseases. In specific situations where the rate of death of host hepatocytes is high, the transplanted cells can repopulate the native liver. Techniques have been established for the large scale isolation, culture, and cryopreservation of human hepatocytes. Shortage of donor organs and the need for immunosuppression are two major hurdles to widespread application of this procedure, and current research in experimental animals is aimed at addressing these problems.