The advent of myocardial metabolic imaging more than 30 years ago ushered in a paradigm shift in the clinical management of patients with ischemic and nonischemic heart disease. A classic example is the so-called metabolic memory of altered glucose and fatty acid metabolism in regions of myocardial ischemia and reperfusion. At the cellular level, metabolic memory is driven by changes in the activities and expression of a host of metabolic enzymes, including reactivation of the fetal gene program. The future of metabolic imaging will require a more-refined understanding of the pathways of metabolic adaptation and maladaptation of the heart. Recent evidence suggests that metabolic signals alter metabolic fluxes and give rise to specific metabolic patterns that, in turn, lead to changes in translational and/or transcriptional activities in the cardiac myocyte. In other words, metabolism provides a link between environmental stimuli and a host of intracellular signaling pathways. This concept has not yet been fully explored in vivo, although metabolic adaptation represents the earliest response to myocardial ischemia and left ventricular remodeling.