With our expanding knowledge of osteoarthritis (OA) over the years, our concept of this "aging" disease has been re-evaluated to that which is the opposite of traditional views. To clinicians and scientists, OA is no longer the inevitable disease of aging, as one conceptualizes gray hair. Epidemiological studies show a higher incidence of OA affecting polyarticular joints in women than age-matched men, particularly those over the age of 55. This discrepancy in sex difference in the OA incidence highlights the significance of sex hormones and their alterations in menopause. Evidence indicates that this alteration possibly occurs early in adult life and may well persist into menopause. As well, this hormonal perturbation is thought to be consequent to obesity in these women. Both in vivo and in vitro studies suggest that estrogen is chondrodestructive via the receptor-mediated mechanism. The finding of estrogen receptor in canine, rabbit, and human articular cartilage further confirms this hypothesis. Recent findings of elevated synovial estradiol level and higher estrogen receptor bindings in human osteoarthritic cartilage strongly suggest the importance of local uptake of estradiol (E2) and the possible up-regulation of estrogen receptors. Estrogen, like other hypothesized etiologies, is important in the development of OA in women.