AbstractAdvancing age will affect every individual and its impact on health deserves significant attention particularly as we address therapeutic possibilities to pathological conditions. The changes that occur in the coronary vasculature as a result of aging‐related senescence set the stage upon which CVD and ischemia can escalate. Because of its importance in health, the consequences of aging on vasculature adaptation must be considered as we identify molecular targets and cell therapies for older patients. To understand the complex relationships between the coronary vasculature and the myocardium, it is important to characterize the unique aged cardiac environment in both locales independent of overlying disease. Therefore, the overall theme of this review is to highlight the biology of aging coronary vasculature and how this promotes a decreased plasticity, exacerbating insults such as ischemia. We will identify potential age‐related mechanisms that may contribute to this overall loss of adaptation and regeneration and review potential therapeutic strategies to ameliorate this dysfunction.