Graves' hyperthyroidism and its main extrathyroidal manifestation, Graves' orbitopathy (GO) are characterized by an increased oxidative stress. Treatment of hyperthyroidism with antithyroid drugs is usually associated with an amelioration of biochemical parameters associated with oxidative stress. Association of antithyroid drugs with antioxidants may favor a prompter control of thyroid hyperfunction. Reactive oxygen species may contribute to the pathogenesis of GO. A recent, large, multicenter, randomized, placebo-controlled clinical trial in patients with mild GO clearly demonstrated that selenium supplementation has beneficial effects on the quality of life and the overall ophthalmic involvement of these patients, while reducing the risk of progression to more severe forms of GO.