Myocardial perfusion reserve is the ratio of global myocardial blood flow at stress vs. rest. Traditionally, it has been measured non-invasively using quantitative positron emission tomography (PET) or cardiac magnetic resonance (CMR). Several recent studies have suggested that measurement of myocardial perfusion reserve provides significant additive prognostic information during stress perfusion imaging in patients with known or suspected coronary artery disease. Myocardial perfusion reserve depends not only on trans-stenotic pressure gradient of the epicardial arteries and thus stenosis severity but even more on the ability of the coronary microvasculature (especially the pre-arterioles) to dilate. Therefore, coronary microvascular dysfunction, which impairs pre-arteriolar function, reduces myocardial perfusion reserve independently of the presence of epicardial coronary stenosis. Hence, the ability to measure myocardial perfusion reserve allows a more comprehensive assessment of the entire coronary circulation, beyond the current paradigm of the epicardial arteries.