Females live longer than males in many species, including humans. This can be explained on the basis of the mitochondrial theory of aging. Mitochondria from females produce significantly less hydrogen peroxide than those from males and have higher levels of mitochondrial reduced glutathione, manganese superoxide dismutase, and glutathione peroxidase than males. Oxidative damage to mitochondrial DNA is also fourfold higher in males than in females. These differences may be explained by estrogens. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the ovariectomy effect. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.