The prevalence of osteoarthritis is higher in women than men, and in women it increases dramatically in the years after menopause. These observations and others reporting a painful form of hand osteoarthritis after the menopause suggest that loss of estrogen at the time of menopause increases a woman's risk of getting osteoarthritis. This article reviews biologic evidence for hormone sensitivity of cartilage, animal studies testing the effect of estrogen on the joints of ovariectomized animals, and human epidemiologic and clinical studies evaluating endogenous estrogen levels and estrogen replacement therapy and their relation to the occurrence of osteoarthritis. Overall the evidence for a role of estrogen in osteoarthritis is conflicting. Epidemiologic studies of women who take estrogen replacement therapy, however, consistently report that these women have a lower prevalence of osteoarthritis than women not taking estrogen, suggesting a possible therapeutic role for estrogen in osteoarthritis.