Rupture of so-called vulnerable or unstable atherosclerotic lesions is responsible for a significant proportion of myocardial infarcts and strokes. However, timely identification of such plaques, in order to allow for aggressive local and systemic therapy, remains problematic. In order to address this problem, there is a need to develop techniques that can image the cellular, biochemical, and molecular components that typify the vulnerable plaque. In this article, both techniques that are in current clinical use and those being evaluated in clinical trials are reviewed with regard to their ability to identify unstable lesions at risk of rupture.