Based on a platform of strong preclinical data, several studies in humans have demonstrated that inhibiting sclerostin with specific antibodies results in a brisk albeit transient anabolic response in the skeleton without an accompanying increase in bone resorption. Impressive increases in bone mineral density and bone strength have been demonstrated. Other than mild injection site reactions, therapy for up to 2years has been well tolerated. The restriction of sclerostin expression almost exclusively to skeletal tissues, coupled with the absence of recognized medical problems in patients with heterozygous sclerostin deficiency, provides promise that the drug can be used safely. Recent results from a Phase 3 fracture trial suggest that anti-sclerostin therapy will be a useful and welcomed new treatment for patients with severe osteoporosis in need of skeletal reconstruction.