In biology and medicine, "translational research" indicates the "translation" from the language of molecular biology in animal experiments to human physiology in order to improve our insight into the molecular mechanisms underlying the progression of cardiac diseases and to verify the mechanism of action or the potential of newly developed drugs. Positron emission tomography (PET) plays a major role in this setting due to four major characteristics: 1) extremely high sensitivity; 2) excellent temporal resolution; 3) the possibility to label molecules without altering their chemical properties and 4) the short half live of isotopes. These features make PET as an unique method able to display in the same image format different variables related to the physiology of the myocardium under different pathophysiological states, thus allowing a more precise geographical correlation of the different processes underlying disease or drug effect. This paper will review the literature available about the utilization of PET in the setting of cardiovascular pathophysiology and drug development. This task will be accomplished by describing the theory and practice of methods available to measure myocardial blood flow and to characterize myocardial metabolism in order to obtain a more precise clarification of disease phenotype. Similarly the potential of this method in defining drug effectiveness in clinical trial will be discussed, in order to offer an overview of the potential for the noninvasive measurement of physiological variables in the modern medicine.