Survival of vertebrate embryos depends on their ability to assemble a correctly patterned, integrated network of blood vessels to supply oxygen and nutrients to developing tissues. The arrangement of larger caliber intraembryonic vessels, specification of arterial-venous identity, and proper placement of major branch points and arterial-venous connections are all precisely determined. A number of recent studies in both mammalian and nonmammalian vertebrate species, reviewed here, have now begun to reveal the major role played by genetically predetermined extrinsic cues in guiding the formation of early embryonic blood vessels and determining the global pattern of the vasculature.