The first step in the prevention of cardiovascular disease is healthy lifestyle and diet. Recent systematic reviews of observational studies ranked Mediterranean diet as the most likely dietary model to provide cardiovascular protection. This review updates the knowledge on the effects of Mediterranean diet from observational and randomized trials published in the last year. The results of the PREDIMED study, a randomized trial providing a higher level of scientific evidence than cohort studies, confirmed that the Mediterranean diet reduces the incidence of cardiovascular events. This effect may be exerted by reducing blood pressure; improving glucose metabolism, lipid profile, and lipoprotein particle characteristics; and decreasing inflammation and oxidative stress. It may also stem from a favorable interaction between diet and gene polymorphisms related to cardiovascular risk factors and events. These recent results allow us to recommend Mediterranean diet to subjects at high risk for cardiovascular disease with the highest level of scientific evidence.