Osteoporosis is frequent in postmenopausal women and old men. As with other prevalent disorders, it is the consequence of complex interactions between genetic and acquired factors. Candidate gene and genome-wide association studies have pointed to several genes as determinants of the risk of osteoporosis. Some of them were previously unsuspected and may help to find new therapeutic targets. Several drugs already available are very effective in increasing bone mass and decreasing fracture risk. However, not all patients respond properly and some of them suffer fragility fractures despite therapy. Investigators have tried to identify the genetic features influencing the response to antiosteoporotic therapy. In this article we will review recent data providing insight into new genes involved in osteoporosis and the pharmacogenetic data currently available.