Odanacatib is a cathepsin K inhibitor developed for the treatment of postmenopausal osteoporosis. It is a bone resorption inhibitor, but which preserves bone formation to some extent. It can be administered once a week, in tablets also containing vitamin D. In a large clinical development program, it has been shown that odanacatib reduces bone resorption, with a reduction of about 60-70% in biochemical markers of resorption, while bone formation decreases to a lesser magnitude. Odanacatib continuously increases bone mineral density (BMD) at the hip and lumbar spine over 5 years. Once it is stopped, a complete resolution of effect is observed, with declining BMD and increased bone turnover. Bone microarchitecture and bone strength have also been improved in clinical trials using quantitative computed tomography (QCT) at the lumbar spine and hip, and high resolution peripheral QCT at the distal radius and tibia. In a phase III trial involving 16,713 postmenopausal women ⩾65 years of age with low BMD, the risk of fragility fracture was significantly reduced at the spine, hip and other nonvertebral sites compared with the placebo group. Odanacatib has been generally well tolerated, with no observation of osteonecrosis of the jaw so far, but with exceptional observations of subtrochanteric atypical fracture and morphea-like lesions. Odanacatib appears a useful new option in the treatment of postmenopausal osteoporosis.