Bisphosphonates have been available for more than a decade. Currently, 4 bisphosphonates--alendronate, risedronate, ibandronate, and zoledronic acid--are approved in the United States. Alendronate and risedronate are oral agents, ibandronate is available in oral and intravenous formulations, and zoledronic acid is an intravenous drug. This review summarizes results from pivotal clinical trials in which these bisphosphonates have been shown to reduce risk for osteoporotic fractures. Also reviewed are results of "bridging" studies designed to demonstrate the comparable efficacy of less frequent dosing regimens to increase bone mineral density and to reduce bone turnover. Compared with placebo controls, all 4 approved bisphosphonates reduce the relative risk of new vertebral fractures in women with postmenopausal osteoporosis. Alendronate, risedronate, and zoledronic acid reduce the relative risk of new nonvertebral and hip fractures. Clinical trial extensions of up to 10 years with alendronate and 7 years with risedronate have shown that efficacy is maintained during long-term treatment.