Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing a person to an in-creased risk of fracture. The overall rate of osteoporosis is increasing annually around the world, especially among the elderly people, resulting in heavier social-economic burden. Till now, certain anti-osteoporosis medications have been ap-plied to prevent and/or treat osteoporosis by the mechanism of either decreasing excessive bone resorption or promoting bone formation. However, the efficacy of those therapies varies among people, sometimes causing unnecessary medical cost or even unwanted side-effects. Therefore, more cost-effective and subject-specific prevention and treatment of osteo-porosis is needed. In such context, pharmacogenomic studies of osteoporosis are of particular importance since it has been widely shown that genetic factors play a role in the efficacy of osteoporosis treatment. The goal of osteoporosis pharma-cogenomics is to optimize drug development and customize per sonalized treatment according to the specific genetic background. Herein, we discussed the application of genetic and genomic approaches to osteoporosis clinics, which held the promise to revolutionize the way we understand, prevent and treat osteoporosis.