Molecular imaging studies have shed light on important biological aspects of atherosclerosis, and are now entering the clinical arena for the detection of clinical atheroma. This review first discusses fundamental principles regarding the rationale for and development of molecular imaging technologies for investigating atherosclerosis. Next, we highlight clinically promising imaging strategies that illuminate key biological aspects of atherosclerosis, including macrophage activity, protease activity, lipoprotein presence, apoptosis, and angiogenesis. We envision that several molecular imaging approaches will become important adjuncts to the clinical management of high-risk atherosclerosis.