The aim of this paper was to systematically review and analyze the epidemiological evidence on the role of Mediterranean diet (MD) in the prevention of cardiovascular diseases (CVD). Fifty-eight studies exploring the relation between MD and lipoprotein concentration, antioxidative capacity and inflammatory markers, hypertension, obesity, diabetes, and metabolic syndrome, were identified and selected. These included 33 cross-sectional, 9 cohort, and 16 intervention studies. Most of the studies showed favorable effects of MD on CVD, although a certain degree of controversy remains in the respect of some issues, as obesity. Important methodological differences and limitations in the studies make difficult to compare results, thus further studies, particularly randomized clinical trials, are needed to finally substantiate the benefits of MD and to shed some lights on mechanisms.