Reactive oxygen species (ROS) are produced by cellular metabolic reactions, and have been implicated in the pathogenesis of several diseases, including atherosclerosis, cancer, and Alzheimer's disease. Interestingly, clinical and epidemiologic studies have, in some cases, indicated that antioxidant nutrients may be effective in disease prevention. However, the efficacy of specific antioxidants in disease prevention is often both controversial and inconclusive. In an effort to elucidate the role of ROS and antioxidants in disease development and prevention, the chemistries of ROS and antioxidants have been examined extensively. Recently, molecular and cellular approaches have demonstrated that ROS and antioxidants can directly affect the cellular signaling apparatus and, consequently, the control of gene expression. This new research provides the link between ROS and antioxidant chemistries and the mechanisms of disease processes and prevention. This review illustrates how ROS function as potential intracellular and extracellular signaling molecules and how antioxidants can affect this process.