Over the past decade, significant progress has been made in the development of novel imaging strategies focusing on the biology of the vessel wall for identification of vulnerable plaques. While the majority of these studies are still in the pre-clinical stage, few techniques (e.g., (18)F-FDG and (18)F-NaF PET imaging) have already been evaluated in clinical studies with promising results. Here, we will briefly review the pathobiology of atherosclerosis and discuss molecular imaging strategies that have been developed to target these events, with an emphasis on mechanisms that are associated with atherosclerotic plaque vulnerability.