Heart disease remains the leading cause of mortality in the United States despite recent reductions in the death rate. Complications of coronary artery disease and its sequelae are the most common mechanism of demise. There have been great advances in the prevention and treatment of acute myocardial infarction, and the literature is replete with articles on attempted localization of so-called vulnerable plaques and vulnerable or high-risk patients to find either that high-risk plaque or that individual before the event. Unfortunately, the search for the so-called vulnerable plaque is hampered by the lack of both natural history studies and proven local or regional therapies for these otherwise asymptomatic plaques. Although emphasis on the vulnerable or high-risk patient is appropriate, identifying these individuals in primary prevention is difficult. This article highlights insights into the pathophysiology of vulnerable plaque and presents a perspective on current treatments, improved risk stratification, and potential technologic advances that might affect future diagnosis and management.