Connexins (Cxs) constitute a large family of transmembrane proteins that form gap junction channels, which enable the direct transfer of small signaling molecules from cell to cell. In blood vessels, Cx channels allow the endothelial cells (ECs) to respond to external and internal cues as a whole and, thus, contribute to the maintenance of vascular homeostasis. While the role of Cxs has been extensively studied in large arteries, a growing body of evidence suggests that they also play a role in the formation of microvascular networks. Since the formation of new blood vessels requires the coordinated response of ECs to external stimuli, endothelial Cxs may play an important role there. Recent studies in developmental and pathologic models reveal that EC Cxs regulate physiological and pathological angiogenesis through canonical and noncanonical functions, making these proteins potential therapeutic targets for the development of new strategies aimed at a better control of angiogenesis.