Resveratrol is a polyphenolic compound found in several plants. In the last decades, the interest in this compound has enormously increased after benefits on metabolism and increased lifespan of various organisms have been reported with its supplementation. Several in-vitro and animal studies have observed that resveratrol can act on multiple molecular targets, including sirtuins, a class of NAD+ -dependent deacetylases. Despite the enthusiastic results reported in many animal- and in-vitro studies, few trials have been performed in humans with contrasting results. These conflicting data may be due at least in part to differences in the characteristics of the patients enrolled, the dosages and the duration of supplementation. Furthermore, many questions remain still unsolved, such as the dose or the duration of treatment to maximize its effects, the bioavailability of resveratrol and the role of food matrix to improve its bioactivity.In conclusion, at present the use of resveratrol as a supplement is not yet justified by the existing evidence.