Diabetic retinopathy, a devastating ocular complication of diabetes mellitus, is the leading cause of blindness among working-age adults in the United States and is a serious public health problem throughout the world. Standard treatment is retinal laser photocoagulation, which is an invasive procedure with considerable limitations and adverse effects. Understanding the biochemical changes and molecular events that occur with diabetes as well as with retinopathy could lead to new and effective treatments. Research indicates an association between oxidative stress and the development of complications from diabetes, including retinopathy. Thus, many sites and sources of oxidative stress that may be involved in the development of diabetic retinopathy have been studied. However, in clinical trials, classic antioxidants have not been beneficial for patients with diabetes. Additional studies are needed to identify treatments that selectively target oxidative stress-mediated protein modification and thus prevent or at least delay diabetic retinopathy.