Endothelial cells (ECs) line blood vessels, i.e. vital conduits for oxygen and nutrient delivery to dis-tant tissues. While mostly present as quiescent “phalanx” cells throughout adult life, ECs can rap-idly switch to a migratory “tip” cell and a proliferative “stalk” cell, and sprout into avascular tissue to form new blood vessels. The angiogenic switch has long been considered to be primarily or-chestrated by the activity of angiogenic molecules. However, recent evidence illustrates an in-strumental role of cellular metabolism in vessel sprouting, whereby ECs require specific metabolic adaptations to grow. Here, we overview the emerging picture that tip, stalk, and phalanx cells have distinct metabolic signatures, and discuss how these signatures can become deregulated in pathological conditions, such as in cancer.