Patterns of cancer vary regionally, with a preponderance of cancers of the lung, breast, large bowel, uterine corpus, and prostate in developed countries, contrasted by a preponderance of cervical, mouth/pharynx, esophageal, and liver cancers in the developing world. Smoking exposes lipids, proteins, and nucleic acids in the lungs and upper aerodigestive tract to oxidants. Lung tissue is exposed to a relatively high concentration of oxygen by virtue of its role in oxygenation of the body. Thus, oxidative stress is important in the etiology of tobacco-related cancers and lung cancer. However, all cells are exposed to oxidative stress, and thus oxidation, and free radicals, may be important in carcinogenesis at multiple tumor sites. Evidence suggests that free radicals may play a role in the initiation of carcinogenesis. Free radical metabolites of many known carcinogens may initiate carcinogenesis by direct DNA damage. Also, by-products of lipid peroxidation, including malondialdehyde and lipid peroxides, are mutagenic and may be carcinogenic. Lipid peroxidation compromises cellular membranes, which may affect the activity of membrane-bound enzymes, many of which are involved in the activation and detoxification of carcinogens. Because our antioxidant defense systems are not completely efficient, it has been proposed that increasing dietary antioxidants may be important in diminishing the cumulative effects of oxidative damage over the long human life span. Considered are the nutrients β -carotene, vitamins C and E, and selenium. There is overview of epidemiologic studies of antioxidant nutrients and cancer. On antioxidant nutrients and cancer prevention, mentioned are observational studies and intervention trials on colon/rectum, oral cavity, lung, esophagus/stomach, bladder, uterine cervix, and skin. The chapter delves into the issue of the effects of antioxidant nutrients and other dietary factors on survival in cancer patients, and emphasis is put on seeking explanation for the apparently discordant findings of observational studies versus intervention trials.