Polyphenols, occurring in fruit and vegetables, wine, tea, extra virgin olive oil, chocolate, and other cocoa products, have been demonstrated to exert beneficial effects in a large array of disease states, including cancer, cardiovascular disease, and neurodegenerative disorders. Many of the biological effects of polyphenols have been attributed to their antioxidant properties, either through their reducing capacities per se or through their possible influences on intracellular redox status. As such, polyphenols may protect cell constituents against oxidative damage and have been reported to limit the risk of various degenerative diseases associated with oxidative stress, including cardiovascular diseases, type 2 diabetes, and cancer. However, accumulating evidence suggests that the classical hydrogen-donating antioxidant activity is unlikely to be the sole explanation for their cellular effects in vivo. Indeed, it has recently become clear that, in complex biological systems, polyphenols are able to exhibit several additional properties which are yet poorly understood. It is evident that polyphenols are potent bioactive molecules and a clear understanding of their precise mechanisms of action as either antioxidants or modulators of cell signaling is crucial to the evaluation of their potential as chemopreventive or anticancer agents and inhibitors of neurodegeneration.