Pluripotent cells can be isolated from the mammalian inner cell mass (ICM) of the embryo at the blastocyst stage, and maintained in culture as undifferentiated, embryonic stem cells (ES). These cells are an important model of mammalian development in vitro and are the focus of a great deal of research for their use in Cell Therapy. In vivo, shortly after the blastocyst stage, the ICM segregates into two layers: the hypoblast which will give rise to the yolk sac, and the epiblast. Epiblast stem cells, like ES cells, are pluripotent. The epiblast will differentiate very early into germ cell progenitors, the primordial germ cells (PGC). PGCs can give rise to embryonal carcinoma cells, the pluripotent stem cells of testicular tumors. During normal embryo development, PGCs migrate into the aorta-gonad-mesonephros region (AGM). Interestingly, this region also harbors the first wave of embryonic hematopoiesis. Subsequent waves of hematopoiesis involve AGM-hematopoietic stem cell (HSC) colonization of the fetal liver, thymus, spleen and ultimately, for adult hematopoiesis, the bone marrow (BM). The BM is also source of mesenchymal stem cells (MSCs). It is accepted that the AGM region cells give rise to the mesothelial cells which are the embryonic precursors of the HSC and MSC of the BM. Recent identification of a subpopulation of cells with markers typical of PGCs in the adult BM, which are capable of differentiating into HSCs, suggests that HSCs originate from a common precursor of PGCs and HSCs derived from the epiblast. Several groups have described the presence of stem cells with the same markers in epidermis, bronchial epithelium, pancreas, retina, hair follicle, heart and dental pulp among, other organs. This presence supports the hypothesis that during early development, epiblast/germ line-derived cells are deposited in various organs which persist into adulthood. The question remains whether these pluripotent stem cells are only developmental remnants or if they continuously contribute to the renewal of tissues, and thus can be reactivated for tissue regeneration without the need for stem cell transplantation for human cell therapies.