Coronary disease is currently a major cause of disability and mortality in older populations. Due to several factors--including increased noncardiovascular mortality, atypical presentation of coronary events, selective survival, and, possibly, clustering of protective genetic traits--the relative risk associated with almost all risk factors decreases with advancing age. Nonetheless, all available evidences from both observational studies and randomized trials indicate that, due to the higher event rates, the absolute risk reduction yielded by preventive interventions is much greater in the older age segments of populations. Another implication of the complex relationships between risk factors and comorbid conditions in the pathogenesis of coronary-related events and mortality, typical of the elderly subjects, is represented by the multiple effects of treatment for single risk factors, such as the decrease in LDL-cholesterol levels and inflammation markers yielded by statins. Taken together, these factors account for the more favorable cost-effectiveness ratios of preventive interventions in the older, as compared with the middle-aged subjects. On the other hand, the high level of interaction between coexistent risk factors and comorbidity renders a global approach to the prevention of coronary events in older subjects mandatory for physicians, as well as for decision-makers. In fact, a multidimensional assessment--including the evaluation of cognitive, affective and social disturbances--driving a multidisciplinary treatment of risk factors--encompassing behavioral counseling and social support--is essential to improve patients' compliance and to effectively reduce the burden of coronary-related morbidity and mortality in older populations.