The vascular endothelium is highly heterogeneous, with phenotypically and functionally distinct endothelial cell (EC) subtypes, partially driven by distinct metabolic programs. While this heterogeneity is important to maintain the multiple functions of the endothelium during tissue repair, it also contributes to challenges to therapeutically modulate ECs in pathological contexts. While the EC heterogeneity is far from being entirely unraveled, recent advances in single-cell technologies have greatly contributed to the identification of different EC subsets and cell states. In this chapter, we discuss new EC subsets captured by single-cell studies in health and disease, also focusing on metabolic EC signatures. We also highlight how such metabolic signatures could be exploited in therapeutic settings to promote or block angiogenesis.