The liver is one of the major organs in the human body. Severe or prolonged exposure of the liver to different factors may cause life‐threatening disease, which necessitates donor organ transplantation. While orthotopic liver transplantation can be used to effectively treat liver failure, it is an invasive procedure, which is severely limited by organ donation. Therefore, alternative sources of liver support have been proposed and studied. This includes the use of pluripotent stem cell‐derived hepatocytes as a renewable source of cells for therapy. In addition to cell‐based therapies, in vitro engineered liver tissue provides powerful models for human drug discovery and disease modeling. This review focuses on the generation of hepatocyte‐like cells from pluripotent stem cells and their application in translational medicine. Stem Cells 2016;34:1421–1426
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