Denosumab is the first fully human monoclonal antibody that inhibits the formation, function, and survival of osteoclasts by blocking the interaction of receptor activator of nuclear factor-κB (RANK) ligand with its osteoclastic receptor RANK. Clinical studies have shown that the decreased bone resorption and increased bone mineral density resulting from the use of denosumab 60 mg twice yearly entail significant risk reduction of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis, with an acceptable rate of side effects so far. Following its approval by the US Food and Drug Administration and the European Medicines Agency, a number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab offers a new choice for the treatment of postmenopausal osteoporosis in patients at high risk for fracture.