Hematopoietic stem cells (HSCs) are tissue specific stem cells that replenish all mature blood lineages during the lifetime of an individual. Hematopoietic cell clusters in the aorta of vertebrate embryos play a pivotal role in the formation of the adult blood system. Recently, people have learned a lot about the embryonic HSCs on their development and homing. During their differentiation, HSCs are regulated by the transcription factors, such as Runx1 and Notch signaling pathway, etc. MicroRNAs also regulate the self-renewal and differentiation of hematopoietic stem/progenitor cells on the post-transcriptional levels. Since the onset of circulation, the formation of HSCs and their differentiation into blood cells, especially red blood cells, are regulated by the hemodynamic forces. It would be of great significance if we could treat hematologic diseases with induced HSCs in vitro on the basis of fully understanding of hemotopoietic stem cell development. This review is focused on the advances in the research of HSCs' development and regulation.