Atherosclerosis is a systemic disease of the vessel wall that mainly affects medium- and large-sized arteries, and accounts for 50% of all deaths in western countries. Imaging of atheromatous plaques has traditionally centered on assessing the degree of luminal narrowing. More recently it has become clear that it is of the utmost importance to identify the vulnerable atherosclerotic plaques responsible for the majority of life-threatening syndromes. Molecular imaging using nuclear medicine techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET), has the potential to characterize the activity of atheromas. In the present review we summarize the results of radionuclide imaging in the detection of vulnerable atherosclerotic lesions.