Flavonoids are widely distributed in nature and a prevalent component of the human diet. Numerous biological activities have been reported. Some clinical trials or meta-analyses have suggested positive associations between flavonoid intake and human health, whereas others have not supported such a relationship. We currently highlight some responses that may be relevant to cancer chemoprevention, including antioxidation, anti-inflammation, and effects on NK cells. In addition, the prooxidant capacity of flavonoids may be relevant for the treatment of cancer. As is the case with other phytochemical constituents found in the diet, many questions over-shadow the results obtained with in vitro studies that do not take into account the ramifications of poor bioavailability, rapid and extensive metabolism, and physiologically relevant concentrations. To overcome some of these difficulties, greater emphasis has been placed on the study of methoxylated flavonoids, which may demonstrate more favorable pharmacokinetic properties. In terms of drug development, newer approaches such as nanotechnology could be useful. It is clear that flavonoids or flavonoid derivatives offer value for the chemoprevention of cancer. Many avenues of development are available and necessary for exploiting the impact on human health.