Several beverages and foods of vegetable origin employed for human consumption contain phenolic compounds, among which one of the most active is resveratrol (3,4’,5-trihydroxystilbene), which is present in high concentrations in red grapes, mulberries, blueberries, and peanuts. Epidemiological studies have shown that resveratrol is involved in many of the health benefits ascribed to the consumption of red wine and several reports have also suggested that it can prevent or slow the progression of a variety of illnesses, including cancer, cardiovascular diseases and ischemic injuries, as well as enhance stress resistance. One major biological property of resveratrol is its antioxidant activity to counteract reactive oxygen species, which are thought to play a key role in the pathogenesis and/or progression of several diseases, causing reversible and/or irreversible oxidative modifications on sensitive macromolecules. In vitro and in vivo evidences suggest that resveratrol can suppress pathological increases in the peroxidation of lipids and other macromolecules, but the mechanism is not yet clear. There is growing interest in the chemopreventive properties of resveratrol, in particular about glioma. Resveratrol was shown to elicit cancer chemopreventive effects in different systems based on its ability to inhibit cellular pathways in vitro associated with tumor development, including initiation, promotion, and progression. This is accomplished by its ability to inhibit COX-1 and COX-2 in vitro and, possibly, COX-2 gene expression, to induce cell cycle arrest and apoptosis in vitro in human malignant cells, including glioblastoma cells, and to suppress VEGF in vitro. Glioma cells at the tumor-invasive front overcome the extracellular matrix (ECM) barrier and penetrate adjacent healthy brain structures. This mechanism partly depends on matrix metalloproteinases (MMPs) activity, degrading ECM components, and by secreted protein acidic and rich in cysteine (SPARC), whose counteradhesive properties mediate cells-microenvironment interactions. Resveratrol significantly and dose-dependently lowered mRNA and protein MMP-2 levels in glioblastoma cells, and induced a dose-dependent downregulation of SPARC gene and protein expression, suggesting this as a relevant molecular mechanism of glioma chemoprevention. Some studies suggest that resveratrol could serve as a chemopreventive agent in human cancers by various mechanisms. However, most of the findings obtained so far arise from in vitro treatment of cells/tissues or from animal models of chemically-induced carcinogenesis, thus demonstrating that resveratrol shows great promise in the treatment of the leading causes of morbidity and mortality in humans. Differently, several other studies found that resveratrol was ineffective in inhibiting tumor growth in animal models despite its ability to inhibit cancer cell growth in vitro. In conclusion, the combination of resveratrol and other anti-glioma therapies may represent a further novel therapeutic strategy to be explored for the treatment of malignant gliomas, whose outcome still remains poor due to the difficulty in removing the invasive growth tumor radically. Despite the large volume of positive data from cultured cells and animal models, there has been limited clinical evaluation of the efficacy of resveratrol as a chemotherapeutic agent in humans cancers. The results of randomized clinical trials currently in progress will (or will not) corroborate the hypothesis that supplementation with resveratrol has effect in chemoprevention of gliomas and other human cancers.