Replenishment of artery cells to repair or create new arteries is a promising strategy to re-vascularize ischemic tissue. However, limited understanding of cellular and molecular programs associated with artery (re-)growth impedes our efforts towards designing optimal therapeutic approaches. In this review, we summarize different cellular mechanisms that drive injury-induced artery regeneration in distinct organs and organisms. Artery formation during embryogenesis includes migration, self-amplification, and changes in cell fates. These processes are coordinated by multiple signaling pathways, like Vegf, Wnt, Notch, Cxcr4; many of which, also involved in injury-induced vascular responses. We also highlight how physiological and environmental factors determine the extent of arterial re-vascularization. Finally, we discuss different in vitro cellular reprogramming and tissue engineering approaches to promote artery regeneration, in vivo. This review provides the current understanding of endothelial cell fate reprogramming and explores avenues for regenerating arteries to restore organ function through efficient revascularization.