Calcitonin is a powerful inhibitor of osteoclast activity that exerts a rapid, transient, and reversible inhibition of bone resorption. Prolonged administration of parenteral calcitonin, by injections of 100 IU every 1 or 2 days, can prevent postmenopausal or postovariectomy bone loss, and is also able to increase trabecular bone mass among patients presenting an established osteoporosis. Prolonged treatment with calcitonin injections is, however, difficult to maintain over the long run. In addition to the ease of administration compared with the injectable forms, nasal calcitonin is much better tolerated, the side effects being rare and generally negligible. A prolonged administration of 200 IU intranasal calcitonin acutely inhibits parameters of bone resorption and can increase lumbar spine bone mineral density (BMD) by 1.7%–3.3% after 1 year. Lower doses also appear to be efficient to prevent early postmenopausal bone loss, but the data are conflictual. The results are more consistent in patients who already suffer from established osteoporosis. The increase in lumbar spine BMD is in the order of 1%–2% after 1 year with 200 IU daily. A therapeutic benefit of calcitonin at the level of the cortical bone has been less well demonstrated than for the trabecular bone. As for other antiosteoporotic therapies, the effect of calcitonin on the reduction of fracture risk has been examined less than the beneficial effect on trabecular bone mass. Currently, there is still no prospective, placebo-controlled study with a sufficient number of patients that demonstrates that long-term parenteral calcitonin administration reduces the risk of osteoporotic fractures. The efficacy of nasal calcitonin treatment to reduce vertebral fracture rate has been best examined in the PROOF (Prevent Recurrence of Osteoporotic Fractures) study. This was a prospective 5-year, placebo-controlled, dose-response study of nasal calcitonin (100, 200, or 400 IU daily). The increase in lumbar spine BMD was modest but significant and not clearly dose dependent, as was the reduction in bone turnover. The relative risk of developing new vertebral fractures was reduced by 33% at the end of the study in the 200-IU dose group (relative risk = 0.67, 95% CI 0.47–0.97, p = 0.03). There was also a nonsignificant reduction in the risk of hip fracture in this dose group. The doses of 100 and 400 IU of calcitonin also reduced the vertebral fracture risk, but the difference did not reach the classical level of statistical significance. A possible effect of calcitonin to enhance bone quality, which cannot be assessed by routinely available methods, is currently being investigated in a prospective placebo-controlled trial that could provide a rational explanation for these effects of calcitonin on the reduction in the vertebral fracture rate without much increase in bone mass or a marked reduction in bone turnover.