The reproducible pattern of blood vessels formed in vertebrate embryos has been described extensively, but only recently have we obtained the genetic and molecular tools to address the mechanisms underlying these processes. This review describes our current knowledge regarding vascular patterning around the vertebrate midline and presents data derived from frogs, zebrafish, avians, and mice. The embryonic structures implicated in midline vascular patterning, the hypochord, endoderm, notochord, and neural tube, are discussed. Moreover, several molecular signaling pathways implicated in vascular patterning, VEGF, Tie/tek, Notch, Eph/ephrin, and Semaphorin, are described. Data showing that VEGF is critical to patterning the dorsal aorta in frogs and zebrafish, and to patterning the vascular plexus that forms around the neural tube in amniotes, is presented. A more complete knowledge of vascular patterning is likely to come from the next generation of experiments using ever more sophisticated tools, and these results promise to directly impact on clinically important issues such as forming new vessels in the human body and/or in bioreactors.