The cardiovascular system plays a crucial role in vertebrate development and homeostasis. Several genetic and epigenetic mechanisms are involved in the early development of the vascular system. During embryonal life, blood vessels first appear as the result of vasculogenesis, whereas remodeling of the primary vascular plexus occurs by angiogenesis. Many tissue-derived factors are involved in blood vessel formation and evidence is emerging that endothelial cells themselves represent a source of instructive signals to non-vascular tissue cells during organ development. This review article summarizes our knowledge concerning the principal factors involved in the regulation of vascular morphogenesis.