Atherosclerosis is the process underlying coronary artery disease, myocardial infarction and cerebrovascular disease and is a leading cause of morbidity and mortality in industrialized countries. The atherosclerotic plaque is often indolent and progressive and may destabilize without warning. Components of the atherosclerotic plaque, including structural, cellular and molecular characteristics, determine its vulnerability to rupture. The imaging techniques currently available utilize invasive and non-invasive methods to characterize coronary artery stenoses. Detection, however, usually occurs late in the course of disease after symptoms have presented. Much effort has recently been directed at early detection and in defining markers of atherosclerotic disease. Our challenge for the future is to find non-invasive imaging modalities that can predict plaque vulnerability before irreversible damage has occurred. Through early detection and a targeted treatment strategy we hope to reduce the burden of ischemic heart disease.