Epidemiological and experimental studies have revealed that a mild to moderate drinking of wine, particularly red wine, attenuates the cardiovascular, cerebrovascular, and peripheral vascular risk. However, the experimental basis for such health benefits is not fully understood. The cardioprotective effect of wine has been attributed to both components of wine: the alcoholic portion and, more importantly, the alcohol-free portion containing antioxidants. Wines are manufactured from grapes, which also contain a large variety of antioxidants, including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol is mainly found in the grape skin, whereas proanthocyanidins are found only in the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin are the major compounds present in grapes and wines responsible for cardioprotection. The purpose of this review is to provide evidence that grapes, wines, and resveratrol are equally important in reducing the risk of morbidity and mortality due to cardiovascular complications. Both wines and grapes can attenuate cardiac diseases such as atherosclerosis and ischemic heart disease. Recently, wine was also found to increase life span by inducing longevity genes. It appears that resveratrol and proanthocyanidins, especially resveratrol, present in grapes and wines play a crucial role in cardioprotective abilities of grapes and wines.