Stem cells are defined as having the ability to self-renew and to generate differentiated cells. During embryogenesis, cells are initially proliferative and pluripotent and then they gradually become restricted to different cell fates. In the adult, tissue stem cells are normally quiescent, but become proliferative upon injury. Knowledge from developmental biology and insights into the properties of stem cells are keys to further understanding and successful manipulation. Here, we first focus on ES cells, then on embryonic development, and then on tissue stem cells of endodermally derived tissues, particularly the liver and pancreas.