The scope of recent literature on the concept of "vulnerable plaque" was reviewed by examining 463 abstracts of primary and review articles identified through MEDLINE (2003 to April 2010). Proposed definition criteria of vulnerable plaque included active inflammation, a thin cap with a large lipid core, endothelial denudation, fissured cap, severe stenosis, or combinations of these findings. In 242 primary studies, histopathology, biomarkers, and imaging of carotid and coronary artery plaques were evaluated for features suggestive of vulnerability. Notably, 89% of these studies were cross-sectional in design and were exclusively conducted in patients with known cardiovascular disease. None of the imaging studies documented whether the identified lesions were responsible for cardiovascular events. Cross-sectional design precludes evaluation of the predictive utility of biomarkers. Because vulnerable plaque is not an established medical diagnosis, no studies have been done that explicitly evaluate the treatment of vulnerable plaques. Few studies examined potential systemic treatments (for example, statins) to modify vulnerability features. Large prospective studies in patients with and without previous cardiovascular events during long follow-up are required to validate this concept.