The current focus of cardiovascular medicine is on early detection and prevention of disease, to control the escalating costs of health care. To achieve this goal, novel imaging approaches that allow for early detection of disease and risk stratification are needed. Traditionally, the diagnosis, monitoring, and prognostication of cardiovascular disease were based on techniques that measured changes in metabolism, blood flow, and biological function. Molecular imaging is emerging as a new tool for the noninvasive detection of biological processes that can differentiate and characterize tissues before manifestation of gross anatomical features or physiological consequences. Leading the way are techniques involving high-sensitivity radiotracers that could revolutionize current diagnostic paradigms. This Review provides an overview of selected molecular-based single photon emission CT (SPECT) and PET imaging strategies for the evaluation of cardiovascular disease-including the evaluation of myocardial metabolism and neurohumoral activity of the heart-and potential future targeted methods of evaluating critical molecular processes, such as atherosclerosis, ventricular remodeling after myocardial infarction, and ischemia-associated angiogenesis.