In recent years, numerous cellular and genetic studies have led to a better understanding of the developmental relationship between hematopoietic and endothelial cell lineages. Specifically, tracing cells expressing various genes such as Brachyury, Flk-1, or Scl has delineated the cellular sequence leading to hematopoietic and endothelial cell development from mesoderm. Moreover, in vitro as well as in vivo studies of invertebrate and vertebrate systems have established that hematopoietic and endothelial cells develop from a common progenitor, the hemangioblast. Finally, the presence of the hemangioblast has been confirmed in postnatal mice and humans. Further characterization of the hemangioblast, both embryo and postnatal, will be critical for a better understanding of the molecular events involved in hematopoietic and endothelial cell differentiation as well as for utilizing this cell population for clinical applications.