Atherosclerosis imaging has taken on increasing importance in the understanding of the natural history of coronary artery disease and the processes leading to luminal narrowing, as well as the assessment of disease burden and therapy efficacy. Intravascular ultrasound (IVUS) has emerged as the new gold standard for atherosclerosis imaging because it provides cross-sectional images of both the arterial wall and lumen with excellent resolution, reveals the diffuse nature of atherosclerosis and the involvement of reference segments, and takes into account vessel wall remodeling. In addition to its clinical indications, IVUS is now widely used as the primary efficacy assessment measure of several antiatherosclerotic approaches in randomized clinical trials. Advantages of IVUS include its ability to reveal antiatherosclerotic effects within a relatively short period of time and with a reasonable sample size, which is in contrast to trials assessing angiographic changes or clinical events. IVUS can also help to determine dose-response relationships in the development of novel pharmacologic agents. IVUS is currently the ideal imaging modality for clinical trials of atherosclerosis progression/regression.