As previously showed for the classical self renewing tissues (i.e., bone marrow, gut and skin), rapidly changing concepts about tissue stem cell biology identify the liver as a maturational lineage system capable to generate mature cells (hepatocytes and cholangiocytes) from a resident stem cells compartment localized near the so called Canals of Hering. At present liver transplantation is the only available therapy for end stage liver diseases and there is an ever increasing shortage of donor livers. Thus in the last decades, HPC has becoming the object of many researchers since HPC might offer a new therapeutic approach for controlling the evolution of chronic liver diseases. The aim of the present review is to update readers with the evolving concepts about hepatic stem cells biology, their characterization and isolation methods and finally their therapeutic potential.