Flexibility in myocardial substrate metabolism for energy production is fundamental to cardiac health. This loss in plasticity or flexibility leads to overdependence on the metabolism of an individual category of substrates, with the predominance in fatty acid metabolism characteristic of diabetic heart disease and the accelerated glucose use associated with pressure-overload left ventricular hypertrophy being prime examples. There is a strong demand for accurate noninvasive imaging approaches of myocardial substrate metabolism that can facilitate the crosstalk between the bench and the bedside, leading to improved patient management paradigms. In this article potential future applications of metabolic imaging, particularly radionuclide approaches, for assessment of cardiovascular disease are discussed.