The radical scavenging antioxidants play an essential role in the maintenance of health and prevention of diseases, and a thorough understanding of the action and capacity of antioxidants is critically important. Despite the assumption that antioxidants must exert beneficial effects against oxidative stress, many large-scale randomized controlled trials gave inconsistent and disappointing results on the prevention of chronic diseases. It is now generally accepted that there is no evidence to support the use of non-discriminative antioxidant supplements for prevention of diseases. On the other hand, recent data show that antioxidants may be effective in the prevention and/or treatment of diseases when the right antioxidant is given to the right subject at the right time for the right duration. Now it is accepted that reactive oxygen species (ROS) act as physiologically important signaling messengers as well as deleterious agents. The signaling ROS are produced in a subtly regulated manner, while many deleterious ROS are produced and react randomly. Free radical-mediated lipid peroxidation products which, in contrast to enzymatic oxidation products, are produced by non-specific mechanisms cause oxidative damage, but may also induce adaptive response to enhance the expression of antioxidant enzymes and compounds. This has raised a question if removal of too many ROS by supplementation of antioxidants may upset the cell signaling pathways and actually increase the risk of chronic diseases. However, it is unlikely that antioxidants impair physiologically essential signaling pathways.