Despite recent progress, cardiovascular and allied metabolic disorders remain a worldwide health challenge. We must identify new targets for therapy, develop new agents for clinical use, and deploy them in a clinically effective and cost-effective manner. Molecular imaging of atherosclerotic lesions has become a major experimental tool in the last decade, notably by providing a direct gateway to the processes involved in atherogenesis and its complications. This review summarizes the current status of molecular imaging approaches that target the key processes implicated in plaque formation, development, and disruption and highlights how the refinement and application of such tools might aid the development and evaluation of novel therapeutics.