The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. In the past few years, compelling evidence accumulated that dysregulation of apoptosis can lead to embryonal death and is involved in the pathophysiology of various inflammatory and degenerative diseases. Specifically, the occurrence of endothelial cell apoptosis has deleterious effects on the development of the cardiovascular system leading to embryonal death. Moreover, endothelial cell apoptosis counteracts neovascularization in the adult organism. On the basis of these findings, one may consider the regulation of endothelial cell apoptosis as a potential therapeutic target. The induction of endothelial cell apoptosis may limit unwanted neovascularization of tumors. In contrast, the prevention of endothelial cell apoptosis may improve angiogenesis and vasculogenesis in patients with ischemia. The present work critically reviews the existing data that supports a role of endothelial cell apoptosis for vascular growth and remodeling and provides insights into the mechanisms and the potential therapeutic consequences.