In an aging society with persistent high prevalence of cardiovascular disease (CVD) in the elderly population, the health care system is facing an increasing challenge to effectively care for these patients. However, due to the under-representation of CVD patients over 75 years of age in clinical trials, assessing safety and efficacy of diagnostic and therapeutic approaches, the evidence for managing elderly CVD patients is especially limited. Physiological changes of aging intertwined with pathophysiology of CVD, and comorbid conditions often complicate clinical management. With the rapid adoption in older patients of invasive cardiovascular procedures, such as percutaneous coronary intervention and trans-catheter aortic valve replacement, the magnitude of this challenge is increasing. Understanding key aspects of cardiovascular physiology in older adults can serve as a foundation to guide interpretations of clinical presentation, diagnostic responses, formulating therapeutic strategies, and monitoring clinical efficacy in elderly patients with CVD.