A significant majority of atherosclerotic plaque ruptures occur in coronary arteries exhibiting none or only modest luminal narrowing on coronary angiography. Emerging data suggest the biological composition of an atherosclerotic plaque (vulnerability to rupture) rather than its degree of stenosis or size is the major determinants for acute clinical events. Thus, the pursuit for noninvasive molecular imaging probes that target plaque composition, such as inflammation and/or microcalcification is a creditable goal. 18 F-fluorodioxyglucose (18 F-FDG) is a metabolic probe that can be imaged using positron emission tomography (PET)/computer tomography (CT) technology to target plaque macrophage glucose utilization and inflammation. Vascular plaque 18 F-FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. More recently, another molecular probe 18 F-sodium fluoride (18 F-NaF) was introduced for PET imaging, which targets active microcalcifications in atherosclerotic plaques. Little is known regarding the role of early microcalcification in the initiation and progression of plaque, partly because of lack of a noninvasive imaging modality targeting molecular calcification. 18 F-NaF PET/CT imaging could provide new insights into the complex interaction of plaque, and facilitate understanding the mechanism of plaque calcification. Moreover, when these 2 molecular probes, 18 F-FDG and 18 F-NaF, that target distinct biological processes in an atherosclerotic plaque are used in combination, they may further elucidate the link between local inflammation, microcalcification, progression to plaque rupture, and cardiovascular event.