Grape chemistry is rather complex and some hundreds of compounds have been identified in the genus Vitis (Vitaceae), arising from two main classes of natural products, phenolics and isoprenoids, widely distributed both in food plants and medicinal herbs. In general, secondary metabolites exert a functional role in plant/grapevine ecology, mainly as phytoalexins, compounds involved in defense against pathogens and phytophagies, as well as in tolerance to detrimental abiotic conditions, for instance adverse climate, high UV irradiance, exposure to excess light (photooxidation), water deficit and anthropogenic pollutants. Furthermore, melatonin (N-acetyl-5-methoxytryptamine) has been discovered in grapes. Therefore, despite the preliminary and incomplete reports regarding the melatonin content in grape/wine, its occurrence in these products and its possible synergistic action with the great variety of other grape phytochemicals add new elements to the hypothesis of health benefits associated to a moderate, regular wine consumption and, more in general, to a Mediterranean dietary style. In this work, we briefly review the huge amount of data regarding the biological activities of grape chemicals.