Several naturally occurring constituents have received considerable attention because of their potential antioxidant activity. Consuming a diet rich in natural antioxidants has been associated with prevention from and/or treatment of atherosclerosis. Bioactive components of food, which are of special interest, include the Vitamins E and C, polyphenols, carotenoids-mainly lycopene and beta-carotene, and coenzyme Q10, featured by antioxidant properties. Antioxidant therapy is supposed to be effective in the early stages of atherosclerosis by preventing LDL oxidation and the oxidative lesion of endothelium. This review focuses on the effect of dietary antioxidants pertained to LDL oxidation and to the vascular endothelial dysfunction. Now that the human genome has been completely sequenced, genetic factors involved in oxidation may open new horizons to identify persons at risk for cardiovascular disease, allowing effective dietary intervention strategies to recover normal homeostasis and to prevent diet-related implications. On this basis, current studies on the action of selected antioxidant nutraceuticals on the activity of transcription factors, such as final targets in the signal transduction cascade and gene regulation, may emerge into new treatment concepts.