The incidence of cardiovascular diseases that are related to the atherosclerotic process increases exponentially with age. Organ lesions, the clinical manifestation of atherosclerotic disease, are late events due to complications in the plaque (ulceration, thrombosis, calcification) which are the result of an increased vulnerability to disruption of a previously stable plaque. The higher incidence of age-related clinical events could be explained by a rising sensitivity of plaques to destabilising factors, both parietal and humoral. The increased probability that a plaque in an elderly patient will became vulnerable could be related to those destabilising factors that significantly increase with aging, such as advanced glycation end-products. For these reasons, it seems most important that the analysis of these age-related destabilising factors, rather than those factors that promote the development of early atherosclerotic plaques, should be undertaken. Taking the point of view of a pharmacological intervention, this should eventually lead to a more complete understanding of this process.