Liver development involves the differentiation and interaction of both endoderm and mesoderm cell types. The role of the liver in drug metabolism makes it an important area of medical research. Mimicking embryonic liver development in vitro using human ESCs is a strategy used to differentiate liver cell types. These can then be used as a model playing a role in the development of drugs and the study of their hepatotoxicity and would also have potential for use in cell therapy and regenerative medicine. Differentiated hepatocyte-like cells were found to have more in common with liver cells than those of other organs, including the secretion of albumin and activity of proteins important in drug metabolism, CYP3A and CYP2D6. However the hepatocyte-like cells were found to more closely resemble fetal rather than adult hepatocytesOrganoid differentiation resulted in cells types which in vivo are both endoderm and mesoderm derived cells of the liver. Culture in this 3D system allowed the spontaneous acquisition of polarity by these cells and their formation into structures reminiscent of liver architecture. After treatment with the toxin 4,4′-diaminodiphenylmethane a cell type and structure specific dose response was observed which matches that described in vivo.