Among individuals with cardiovascular risk factors, reductions in coronary vasodilator capacity with or without diabetes mellitus (DM) carry important diagnostic and prognostic information. Positron emission tomography (PET) myocardial perfusion imaging in concert with tracer kinetic modeling allows the assessment of absolute regional myocardial blood flow (MBF) at rest and its response to various forms of vasomotor stress. Such noninvasive evaluation of myocardial flow reserve (MFR) or the vasodilator capacity of the coronary circulation expands the possibilities of conventional scintigraphic myocardial perfusion imaging from identifying flow-limiting epicardial coronary artery lesions to understanding the underlying pathophysiology of diabetic vasculopathy, microcirculatory dysfunction, and its atherothrombotic sequelae. Invaluable mechanistic insights were recently reported with PET by unraveling important effects of insulin resistance, obesity, and DM on the function of the coronary circulation. Such noninvasive assessment of coronary circulatory dysfunction enables monitoring its response to antidiabetic medication and/or behavioral interventions related to weight, diet, and physical activity that may evolve as a promising tool for an image-guided and personalized preventive diabetic vascular care. Whether PET-guided improvement or normalization of hyperemic MBF and/or MFR will translate into improved patient outcome in DM is a laudable goal to pursue next.