Atherosclerosis is a common age-related disorder and is the major cause of morbidity and mortality in the developed countries. Structural imaging techniques, such as CT and MRI, have been of limited value in early detection of atherosclerotic plaques, and therefore, there is a dire need for techniques that are highly sensitive and specific for this purpose. Over the past decade, PET imaging with FDG and NaF has been tested for detection and characterization of atherosclerotic plaques in the major coronary arteries. While FDG uptake reflects inflammation in the plaques, NaF uptake is related to micro-calcification at the site. Recent data have revealed higher sensitivity for NaF compared to that of FDG-PET imaging for assessing this age-related disorder. Therefore, it is conceivable that detection of micro-calcification by NaF may become the study of choice in the future. Also, small volume of plaques even in the major arteries poses a significant challenge for optimal visualization and quantification of the disease process. Based on animal and human data, it has become apparent that global assessment of disease activity may overcome the physical limitations of PET imaging for optimal quantification of plaque burden in the arteries. The role of other tracers for detection of atherosclerosis is limited at this time and it is unlikely that other compounds will play a role in assessing plaques in the near future.