Epidemiological studies suggest that consumption of wine, grape products, and other foods containing polyphenols is associated with decreased risk for cardiovascular disease. The benefits of wine consumption appear to be greater than other alcoholic beverages. Experimental studies indicate that grape polyphenols could reduce atherosclerosis by a number of mechanisms, including inhibition of oxidation of LDL and other favorable effects on cellular redox state, improvement of endothelial function, lowering blood pressure, inhibition of platelet aggregation, reducing inflammation, and activating novel proteins that prevent cell senescence, e.g. Sirtuin 1. Translational studies in humans support these beneficial effects. More clinical studies are needed to confirm these effects and formulate dietary guidelines. The available data, however, strongly support the recommendation that a diet rich in fruits and vegetables, including grapes, can decrease the risk for cardiovascular disease.