Positron emission tomography (PET) with fluorine 18-labeled fluorodeoxyglucose (FDG) has provided important insights into the alterations in myocardial glucose metabolism associated with normal cardiac physiology and pathophysiology. In patients with left ventricular dysfunction caused by coronary artery disease, PET-FDG studies have identified certain patterns of myocardial glucose metabolism relative to flow that are associated with viable myocardium. Consequently, in many centers, PET-FDG imaging is being used to identify patients with left ventricular dysfunction who are likely to benefit from coronary revascularization. However, myocardial glucose metabolism (and thus myocardial uptake of FDG) is markedly dependent on a variety of factors, particularly the substrate environment and level of myocardial perfusion. These and other factors must be considered to obtain and interpret myocardial FDG images accurately with respect to the underlying pathophysiologic process. In this review the impact of these factors on myocardial FDG imaging, as well as the relative advantages and disadvantages of approaches designed to optimize myocardial PET-FDG studies, will be discussed.