Recently, it has been shown in several animal models that more than 90% of host hepatocytes can be replaced by a small number of transplanted donor cells in a process we term therapeutic liver repopulation. This phenomenon is analogous to repopulation of the hematopoietic system after bone marrow transplantation. Liver repopulation occurs when transplanted cells have a growth advantage in the setting of damage to recipient liver cells. Here we review the current knowledge of this process and discuss the hopeful implications for treatment of liver diseases.