Directed differentiation of hepatocytes from induced pluripotent stem cells (iPSCs) holds promise as source material for treating some liver disorders. The unlimited availability of perfectly differentiated iPSC-derived hepatocytes will dramatically facilitate cell therapies. While systems to manufacture large quantities of iPSC-derived cells have been developed, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. This short review highlights important challenges and possible solutions to the current state of hepatocyte biofabrication for cellular therapies to treat liver diseases. Successful cell transplantation will require optimizing the best cell function, overcoming limitations to cell numbers and safety, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new autologous stem cell-based therapies to treat liver diseases.