The notion of cancer prevention through antioxidant intervention arises from the fact that fruits and vegetables contain antioxidants and are linked to low cancer rates in those who consume them. Protection against DNA damage by plant food products can be demonstrated in vitro. However, particular care is needed when measuring the damage, since oxidation readily occurs during sample preparation, creating a serious artefact. In the case of DNA oxidation, estimates of background levels in human cells range over 3 orders of magnitude, depending on the method used. Using validated, reliable biomarker assays for DNA oxidation, it is possible to demonstrate a decrease in oxidative damage after supplementation with isolated antioxidants or whole plant foods in humans. In contrast, in several large-scale interventions with disease or death as the endpoint, supplementation with beta-carotene resulted in no effect or an increase in cancer incidence. It is certainly true that we do not yet fully understand the role of phytochemicals as antioxidants, or as modulators of other processes related to carcinogenesis and its prevention.