Cardiovascular disease represents an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Fortunately, most premature cardiovascular deaths are preventable. Therefore, prevention becomes vital and diet has shown beneficial effects to protect from CVD (CVD). Fruits and vegetables are dietary sources of natural antioxidants and it is generally accepted that antioxidants in these foods are key in explaining the inverse association between fruits and vegetables intake and the risk of developing a cardiovascular event or having elevated levels of cardiovascular risk factors. Available evidence supports the central role of oxidative stress in the atherosclerosis process and the correlation between increased oxidative stress and vascular disease. Theoretically, antioxidants in fruits and vegetables are important in inhibiting oxidative mechanisms that lead to various degenerative diseases including CVD. However, results from many interventional trials using antioxidants given as supplements have not been concordant with previous positive findings from observational epidemiologic cohort studies. The present manuscript gives a brief overview of the relationship between natural antioxidants (specially vitamin C, vitamin E and beta-carotene) intake and the risk of CVD.