In the embryo, blood vessel formation de novo (vasculogenesis) and from existing vessels (angiogenesis) results in blood vessels lined by endothelial cells (ECs). The relationship between ECs and blood cells suggested by their physical closeness was recently confirmed with the demonstration of progenitors that give rise to both cell types. In tumors, new blood vessel formation has been thought to occur primarily via angiogenesis. Recent evidence, however, suggests that postnatal vasculogenesis also contributes to tumor neovascularization. In this article, we provide an update on EC development, including early lineage specification, morphogenesis or differentiation to form functional blood vessels, and regulation of EC survival and senescence. Furthermore, we review the latest findings on tumor neovascularization and therapeutic potentials of molecules critical to this process.