Myocardial perfusion imaging with SPECT/CT or with PET/CT is a mainstay in clinical practice for the diagnostic assessment of downstream, flow-limiting effects of epicardial lesions during hyperemic flows and for risk stratification of patients with known or suspected coronary artery disease (CAD). In patients with multivessel CAD, the relative distribution of radiotracer uptake in the left ventricular myocardium during stress and rest accurately identifies flow-limiting epicardial lesions or the most advanced, so called culprit, lesion. Often, less severe obstructive CAD lesions may go undetected or underdiagnosed the concurrent ability of PET/CT with radiotracer kinetic modeling to determine myocardial blood flow (MBF) in absolute terms (mL/g/min) at rest and during vasomotor stress allows the computation of regional myocardial flow reserve (MFR) as an adjunct to the visual interpretation of myocardial perfusion studies. Adding the noninvasive evaluation and quantification of MBF and MFR by PET imaging to the visual analysis of myocardial perfusion may (1) identify subclinical CAD, (2) better characterize the extent and severity of CAD burden, and (3) assess "balanced" decreases of MBF in all 3 major coronary artery vascular territories. Recent investigations have demonstrated that PET-determined reductions in hyperemic MBF or MFR in patients with subclinical or clinically manifest CAD are predictive of increased relative risk of future cardiovascular events and clinical outcome. Quantifying MFR with PET enables the identification and characterization of coronary vasodilator dysfunction as functional precursor of the CAD process, which offers the unique opportunity to monitor its response to lifestyle or risk factor modification by preventive medical care. Whether an improvement or even normalization of hyperemic MBF or the MFR in subclinical or in clinically manifest CAD confers an improved long-term cardiovascular outcome remains untested. Nonetheless, given the recent growth in the clinical utilization of myocardial perfusion PET, image-guided and personalized preventive care of vascular health may become a reality in the near future.