OBJECTIVE: To review the evidence for use of denosumab for the treatment of postmenopausal osteoporosis. DATA SOURCES: A search of MEDLINE and EMBASE databases was conducted during January 2012, using the terms denosumab and osteoporosis, with index dates of 2000 to 2011. Additional information was gathered from Amgen and references cited in articles retrieved. STUDY SELECTION AND DATA EXTRACTION: English-language articles including clinical trials involving denosumab for treatment of osteoporosis and review articles were reviewed. Articles using denosumab in males or as treatment for conditions other than osteoporosis or osteopenia were excluded. DATA SYNTHESIS: Many clinical trials have supported the safety and efficacy of denosumab in postmenopausal women with bone loss. It has been shown to improve bone mineral density, decrease markers of bone turnover, and prevent new vertebral fractures. It shows improvement over placebo in studies and has at least similar efficacy to alendronate in measurements of bone mineral density, with less risk for osteonecrosis of the jaw and atypical fracture, but with an increased risk of infections and neoplasms. European cost-effectiveness studies have also demonstrated that denosumab is a cost-effective choice compared to risedronate and no treatment for fracture prevention for postmenopausal women with osteoporosis. CONCLUSIONS: Denosumab has demonstrated efficacy and safety as a first-line treatment for postmenopausal osteoporosis in multiple clinical trials over at least 6 years. It may be most cost-effective for women who are unable or refuse to take bisphosphonate drugs.