The hypothesis that arterial wall remodeling permits accumulation of a large atherosclerotic burden before there is any detectable narrowing of the vessel lumen has received support from necropsy and intravascular ultrasound (IVUS) studies. In a series of transplant donors assessed by IVUS, coronary atheromas were found in 17% of those younger than 20 years, 37% of those aged 20 to 29 years, and 60% of those aged 30 to 39 years, whereas angiography results were negative in 97% of this population. Necropsy data indicate a similar age-related prevalence and suggest that atherosclerosis risk factors are operative from a very early age. The IVUS findings show that disease is characteristically diffuse and involves the entire arterial tree, with progression including formation of multiple, potentially rupture-prone plaques that are not associated with vessel stenosis. These findings indicate the need for aggressive and early systemic intervention that targets modifiable risk factors to reduce coronary artery disease morbidity and mortality in the general population.