Dietary interventions are first-line therapy for coronary heart disease prevention and treatment. Increasing scientific evidence suggests that the traditional Mediterranean diet may reduce the risk of cardiovascular disease. The cardiovascular benefits of this whole-diet approach may outweigh those of typically prescribed low-fat diets. The burden of coronary heart disease is enormous, and nutritional approaches that optimize cardiovascular health are essential. Clinical trial evidence supporting the role of the Mediterranean diet in cardiovascular health is presented with an emphasis on the physiological effects of omega-3 fatty acids. Implications for clinical practice and future research are also discussed. The cardio protective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO, polyunsaturated fatty acids (PUFA), and poly phenolic compounds, such as resveratrol, in the human body.