Cellular therapies derived from embryonic stem (ES) cells have acquired new interest and urgency with the demonstration that embryonic stem cells can be established from human blastocyst-stage embryos. Our ability to derive therapeutic cells from differentiating ES cell cultures will ultimately depend on our understanding of the embryonic developmental processes that direct the differentiation of pluripotent cells into transplantable lineage-specific stem cells, and on our ability to recapitulate these processes in vitro. In this review, we evaluate the work that has been done to date on the hematopoietic differentiation of ES cells, and discuss this in the context of what is known about the embryonic origin of the hematopoietic stem cell.