Mainstream and ETS exposure are strong risk factors for cardiovascular disease in men and women. The relationships between smoking and cardiovascular disease result from multiple mechanisms that interact to contribute to atherosclerosis, vascular injury, thrombosis, and vascular dysfunction. We are only now beginning to understand how smoking contributes to the genesis and progression of cardiovascular disease. Because of the complexity of the interactions between nicotine and the components of MSS, ETS, and sidestream smoke with the vasculature, it will take a great deal of time and effort to fully unravel the mechanisms by which smoking contributes to cardiovascular disease. In addition, cardiovascular risk in female smokers is complicated by hormonal variables that may contribute to greater relative risk. It is important that health care providers, educators, and policy makers recognize the changing patterns of smoking and the impact of smoking on cardiovascular disease, and continue campaigns aimed at enhancing smoking cessation in the general population and in teens. Rigorous research is needed on the changing cultural, psychosocial, and environmental factors that influence tobacco use to improve our understanding of racial/ethnic smoking patterns, and identify strategic tobacco control opportunities. The capacity of tobacco control efforts to keep pace with patterns of tobacco use and cessation depends on timely recognition of emerging prevalence and cessation patterns and the resulting development of appropriate community-based programs to address the factors involved. Smoking trends today will determine how heavy the health burden of cardiovascular disease and others will be among communities tomorrow. Programs that aim at early intervention and reflect cultural diversity will be the cornerstone in the battle against tobacco use. Continued interest in research, educational, and prevention efforts are needed to help curb the risk of cardiovascular disease from smoking in men and women.