Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease.