Human embryonic stem cells (hESC) provide access to the earliest stages of human development and because of their high proliferation capability, pluripotency and low immunogenicity may serve as a potential source of specialized cells for regenerative medicine. hESC-derived hepatocyte-like cells exhibit characteristic hepatocyte morphology, express hepatocyte markers and are capable of executing a range of hepatocyte functions. However, there are many challenges and obstacles to be overcome before the use of hESC and hESC-derived hepatocyte-like cells in clinical practice can be realized. Here, we highlight some of the recent efforts in this area, in hope of providing insights toward this complex yet important area of therapeutical modality for treating patients with liver disease.