The concept of the "vulnerable" plaque has recently emerged to explain how quiescent atherosclerotic lesions evolve to cause clinical events. Vulnerable plaques are generally non-obstructive, asymptomatic lesions that may abruptly rupture and induce thrombotic occlusion leading to tissue ischemia and its attendant sequelae. They are responsible for over 50% of cases of sudden death and acute myocardial infarction. The lipid component of vulnerable plaques, which is abundant and highly enriched in oxidized low-density lipoprotein (OxLDL), strongly contributes to their propensity to rupture through physical, inflammatory, and thrombogenic properties. We hypothesized that OxLDL would serve as an ideal target to detect vulnerable plaques. In a series of experimental studies, we have shown that oxidation-specific antibodies (Ox-AB) specifically accumulate in vivo within lipid-rich atherosclerotic lesions but not normal arteries, provide a quantitative measure of the content of OxLDL, allow detection of atherosclerosis progression and regression in the context of enhanced or reduced OxLDL content and non-invasively image atherosclerotic lesions. Ox-AB may be tagged with appropriate labels for use in nuclear scintigraphy, magnetic resonance, or ultrasound imaging. Potential research and clinical applications include studying the natural history of atherosclerosis in animal models and humans, evaluating novel drug or genetic therapies on progression and regression of atherosclerosis, evaluating plaque stability, screening and serial follow-up of high-risk individuals, non-invasive imaging of vulnerable plaques, and assessing the clinical efficacy of new treatments of atherosclerosis.