Over the past 12 years bisphosphonates have become a mainstay of treatment for postmenopausal osteoporosis. As a class, bisphosphonates significantly suppress bone turnover and increase BMD at the lumbar spine and other site through their direct inhibitory effects on osteoclasts. Alendronate and risedronate reduce the incidence of clinical vertebral and non-vertebral fractures. Etidronate and both oral and intravenous ibandronate reduce the incidence of clinical vertebral fractures, but data from primary analyses for reduction in non-vertebral fractures are currently less robust. Intravenous administration of zoledronate is under late-stage investigation for use in postmenopausal osteoporosis. Combinations of alendronate with estrogen or raloxifene provide a greater reduction in bone turnover markers and greater increases in BMD, but fracture risk reduction has not been determined. Overall, bisphosphonates are well tolerated. The most common side effects of oral bisphosphonates are upper gastrointestinal symptoms. Newer safety concerns about the use of bisphosphonates include osteonecrosis of the jaw and oversuppression of bone turnover. The optimal duration of bisphosphonate treatment has not been clearly established. © 2006 Springer Science + Business Media, LLC.