Myocardium is flexible when it comes to energy substrate utilization; it uses fatty acid, glucose, lactones, and ketones for its energy requirement. The myocardial energy substrate preference varies in a dynamic manner depending on myocardial perfusion, energy demand, substrate availability, and local/systemic hormonal changes. The authors discuss the metabolic perturbations seen in insulin-resistant myocardium and how they result in structural and other biochemical changes that ultimately result in left ventricular hypertrophy and diastolic and systolic dysfunction. The authors also discuss the utility of metabolic imaging to study metabolic derangement as seen in insulin-resistant rodents. The role of positron emission tomography and cine-magnetic resonance imaging coregistration in quantifying myocardial glucose uptake is demonstrated in fasted, 13-week old Sprague-Dawley rats under insulin-/glucose-stimulated conditions. This study demonstrates the utility of in vivo, noninvasive positron emission tomography and cine-magnetic resonance imaging modalities to longitudinally follow insulin resistance models during disease progression and after specific interventions.