There is compelling evidence that alterations in myocardial substrate use play a key role in a variety of normal and abnormal cardiac conditions such as aging, left ventricular hypertrophy, and diabetic heart disease. However, it is unclear whether the metabolic changes are adaptive or maladaptive. Development of transgenic models targeting key aspects of myocardial substrate use, such as uptake, oxidation, and storage, is accelerating our understanding of the metabolic perturbations of cardiac disease. However, whether the metabolic phenotype in these models is relevant to the human condition is frequently unknown. The importance of altered myocardial metabolism in the pathogenesis of cardiac disease is underscored by the current robust development of novel therapeutics that target myocardial substrate use. Currently, magnetic resonance spectroscopy, single photon emission computed tomography, and positron emission tomography are the 3 methods available to image myocardial substrate metabolism. In this review the role of metabolic imaging in the study of specific cardiac disease processes will be discussed. Both the current and future capabilities of metabolic imaging to furthering our understanding of cardiac disease are highlighted.