Techniques to identify and treat vulnerable plaques are the focus of enormous research. Some have questioned the benefit of locating individual vulnerable plaque in a multifocal disease. On autopsy, it is found that most deaths are caused by thrombotic occlusion of a single plaque; simultaneous occurrence of 2 occlusive thrombi is rare, but a second vulnerable plaque is common, particularly in acute myocardial infarction (MI). Angiographic progression is poorly predicted by risk factors, and angiographic progression is a weak predictor of MI or death. Intravascular ultrasonography (intravascular ultrasound [IVUS]) studies find plaque rupture in most MI patients and in approximately half with unstable angina, but in only a minority of patients with stable angina. IVUS identifies a second vulnerable plaque in many patients with unstable angina, and in most MI patients. Angioscopy reveals a very low incidence of a second vulnerable plaque compared with angiography and IVUS, but identifies additional yellow plaques in many patients with stable angina and in most patients with unstable angina or MI. Using thermography catheters and a temperature cutoff of 0.1°C, approximately half the patients with stable angina have >1 hot lesion; however, if the cutoff is 0.2°C, only ≈15% have a second hot lesion. New imaging techniques may detect additional characteristics of plaques and new predictive models may assess the risk of vulnerable plaques and patients. This approach enables physicians to "buy time" by application of local therapies until systemic therapies stabilize plaques. This may also reduce the risk in subjects in whom systemic therapies do not work.