Several medications have proved effective in reducing the fracture risk in postmenopausal women with osteoporosis. The optimal duration of use of these medications remains to be established, however. Gains in bone mineral density (BMD) persisted throughout 10years of treatment with alendronate or 7years with risedronate. However, proof of long-term protection against fractures was obtained only for shorter treatment periods, 4years with alendronate and 5years with risedronate. The persistence of treatment effects after drug discontinuation varies across medications, and further studies are needed before this point can be incorporated into treatment decisions. With raloxifene, the BMD effect observed after 3 and 4years persisted when the drug was given for 8years, and the fracture risk reduction was similar after 4years and after 3years. The long-term safety profile also was similar, with a significant decrease in the incidence of invasive estrogen-receptor-positive breast cancer and a persistent increase in the risk of deep vein thrombosis. However, a sharp drop in BMD occurred upon raloxifene discontinuation. Thus, 4years may be appropriate for anti-resorptive drug therapy. However, the optimal treatment duration should be determined on a case-by-case basis according to the results of regular fracture-risk evaluations.