The liver is one of the privileged organs of the human body that has retained extensive self-regenerative capacity. Without the need to activate the stem cell compartment, the adult hepatocytes is capable of undergoing serial replication and is the basis of repair in most acute liver injury. It is also allowed the pioneering of living related transplantation where a donor can donate two thirds of the liver and both the remnant liver and transplanted graft can grow back to its full size and function. However, in many chronic diseases, either due to senescence or toxic effect of the liver mileu, the regenerative capacity of the hepatocyte is arrested and the liver respond by activating a ductular proliferation presumably to repair itself. This in human diseases, is also accompanied by scarring and the eventual development of liver cirrhosis and carcinogenesis, both of which account for top 10 causes of mortalilty in the world. While liver transplantation is curative, the dearth of healthy graft supply is outstripped by demand. With increasing long wait times and spiraling fall off rates on the waiting list, stem cell therapy has held out a hope and panacea for this unmet need. Yet after 30 years of intense research and advances, the clinical translation remains controversial and premature. This review looks at the key milestone and fundamental hurdles that has held up the field.