Liver is a major metabolic organ of the body and is known to comprise of two epithelial cell lineages, namely, hepatocytes and cholangiocytes which are known to originate from hepatoblasts during fetal developing stages. Upon acute injury, the hepatocytes and cholangiocytes undergo cellular division to compensate the loss, however, chronic damage may suppress this proliferative ability and as a consequence hepatic and extra-hepatic stem cells may contribute for liver regeneration. Facultative liver stem cells (oval cells) may emerge, proliferate and contribute in replacing damaged hepatic cells. Similarly, bone marrow and mesenchymal stem cells are also known for contributing in liver regeneration having their ability of self renewal and differentiation. However, a closer look is still required to bridge the existing knowledge gaps between functionality and limitations. Thereby, we have discussed the detailed mechanistic insights of both hepatic and extra-hepatic stem cells including, stem/progenitor cells, adult/fetal hepatocytes, oval cells, bone marrow and mesenchymal stem cells. We have also focused on few in vitro and in vivo studies elucidating therapeutic applications and challenges related to the liver stem cells. We believe that such conversations may provide invaluable contribution for realistic advancement in the state of therapeutic stem-cell transplantation.