Oxidative stress is the result of an imbalance of antioxidants and pro-oxidants. Since toxic free radicals are the result of normal metabolism, their destruction is imperative. Cataracts are the leading cause of blindness worldwide. Opacity of the lens is a direct result of oxidative stress. Cataracts occur primarily due to age, but also are common in diabetes where superoxide in the mitochondria is elevated as a result of hyperglycemia. This review will investigate the risk factors of cataract including diet (vitamins, fat and alcohol) as well as UV light and diabetes. The pathophysiology of lens opacification will be discussed and related to the biochemistry, especially during the aging process and in diabetes. Animal and human supplemental antioxidant studies will be reviewed and the mechanisms discussed for cataract prevention and treatment. New genetic engineering approaches to overexpress antioxidant enzymes have given intriguing results and show promise. Lastly, a new approach to target mitochondrial superoxide with antioxidant molecules will be outlined.