Investigations into the developmental origins of blood cells have indicated that the genes and molecular pathways controlling hematopoiesis are highly conserved among metazoans. In this chapter we summarize the progress in understanding how the molecular mechanisms regulating Drosophila blood development compare with analogous processes in vertebrates. In both Drosophila and vertebrates, the ontogenetic origins of cardiovascular cells and blood cells are closely related. In Drosophila, there is in vivo evidence for the presence of hemangioblast-like cells. Furthermore, there are significant similarities between the molecular mechanisms regulating the development of the lymph gland, the Drosophila hematopoietic organ, and the formation of the mammalian AGM region. Other aspects are also shared, including the sequential maturation of progenitor cell types, the presence of multipotent or stem cell progenitors, and a requirement for a niche interaction to maintain these progenitors. During their development, Drosophila blood cells utilize an array of conserved signaling pathways and transcriptional regulators to mediate cell fate specification and differentiation. The power of Drosophila as a model system is well established and our understanding of hematopoiesis, in both normal and aberrant contexts, will surely illuminate similar mechanisms in vertebrate systems, including humans.