During mammalian ontogeny, hematopoietic activity can be found in distinct anatomical sites, which con-tribute to primitive or definite hematopoiesis. The origin of the hematopoietic stem cell (HSC) has been a controversial issue in the field of hematopoiesis. It has long been believed that the origin derives from the extra-embryonic yolk sac. However, there is now considerable evidence that the first adult repopulating HSC is autonomously generated from a distinct region within the embryonic mesoderm, the aorta-gonad-mesonephros (AGM) region. This review describes the origin and precise location of HSC in the embryo and in AGM region, the hematopoietic microenvironment and the hematopoietic regulatory mechanisms in AGM region.