Endothelial cells (ECs) exhibit a remarkable and unique plasticity in terms of redox biology and metabolism. EC are equipped with a selective and unique repertoire of redox and metabolic mechanisms that play a crucial role to preserve redox balance, and adjust metabolic conditions in both normal and pathological angiogenesis. The identification of such redox signaling and metabolic pathways is crucial to gain of better insights in endothelial biology and dysfunction. We are currently investigating the formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs using different genetic and molecular approaches. These insights will be useful for establishing innovative therapeutic approaches for the treatment of those conditions where aberrant or excessive angiogenesis is the underlying cause of the disease itself.