Positron emission tomography and tracers of blood flow and of metabolism offer a most unique capability: The noninvasive study of regional myocardial metabolism and its derangements as a result of regional or global myocardial disease. Research with PET not only has confirmed the existence of metabolic fluxes and reactions as established previously through highly invasive or even destructive investigational techniques but has provided new insights into pathophysiologic processes, especially in ischemic and post-ischemic myocardium. From these investigations in both animal experiments and in humans, observations have emerged which indicate a place for PET in clinical cardiology. PET is likely to contribute to detection of disease, to characterizing its extent and severity as well as to decide upon the most appropriate therapeutic strategy and assessing its results. It is recognized that many of these observations with clinical implications await confirmation through larger clinical trials, follow-up studies as well as independent confirmation. Besides exploring ischemic heart disease, PET is equally suitable for examining substrate fluxes and interactions in other disorders as for example in intrinsic myocardial disease like primary and secondary cardiomyopathies. While derangements of metabolism in these disorders may be an expression of the consequences of the disease process or its underlying mechanisms itself, findings on PET will allow formulation of new hypotheses on disease mechanisms that conversely can then be tested. In addition to F-18 2-deoxyglucose and C-11 palmitate, the number of tracers for substrate metabolism is likely to increase. An example is C-11 acetate currently intensely investigated as a tool for measuring overall myocardial oxidative metabolism. Others as for example C-11 labeled short chain fatty acids are on the horizon. The study of cardiac receptors is similarly possible. Thus, a set of tools will soon be available for dissection of entire metabolic pathways and for determination of rate limiting steps in health and disease and to more clearly define specific defects in biochemical reaction steps that critically contribute to or even ae the specific cause of disease.