Hematopoiesis represents one of the paradigmatic systems for studying stem cell biology, but our understanding of how the hematopoietic system develops during embryogenesis is still incomplete. While many lessons have been learned from studying the mouse embryo, embryonic stem cells have come to the fore as an alternative and more tractable model to recapitulate hematopoietic development. Here we review what is known about the embryonic origin of blood from these complementary systems and how transcription factor networks regulate the emergence of hematopoietic tissue from the mesoderm. Furthermore, we have performed an integrated analysis of genome-wide microarray and ChIP-seq data sets from mouse embryos and embryonic stem (ES) cell lines deficient in key regulators and demonstrate how this type of analysis can be used to reconstruct regulatory hierarchies that both confirm existing regulatory linkages and suggest additional interactions