The extensive regenerative capacity of hepatocytes and the key roles of the liver in metabolic processes have generated interest in the liver as an appropriate target for cell and gene therapy. If cells were considered as natural biomaterials, then liver cell transplantation would fall within the general field of bioengineering. While unmodified hepatocytes engraft in the liver and ectopic sites, biological modifications and optimization of bioengineered systems would facilitate engraftment and survival of transplanted cells, especially in ectopic locations. Acute liver failure, chronic liver disease and metabolic deficiency states are among the conditions that can potentially be treated by cell transplantation. In acute liver failure, cell transplantation into the liver, along with the creation of an extrahepatic reservoir of cells might be required because engraftment and proliferation of transplanted cells in the liver needs time. In other situations, gradual liver repopulation alone might well be effective without additional manipulations.