Hepatocyte transplantation (HTx) has been developed for use in liver-based metabolic disorders and in acute liver failure. Worldwide, there are around 80 patients that have been transplanted with hepatocytes. Almost all reported studies prove feasibility and safety of the procedure with short- to medium-term success. Availability of good quality hepatocytes (HCs) is the main limiting factor, and therefore alternative sources of cells such as stem cells are being investigated. Other limiting factors include cell engraftment, survival, and function of transplanted cells. It remains to be seen if progress in HTx research can overcome these hurdles leading to the wider use of the technique as an alternative to liver transplantation in the future.