The majority of current therapeutics for osteoporosis is targeting bone resorption by osteoclasts. Bisphosphonates, potent and specific inhibitors of bone resorption, are widely used for postmenopausal osteoporosis on the basis of large scale clinical trials which proved their ability to reduce fracture risk. Estrogen, which had been widely used in the US, lost its position of standard drug therapy for osteoporosis because of the recent evidence of increasing adverse events. On the other hand, the market share of selective estrogen-receptor modulators (SERMs), which utilize valuable functions of estrogen and have less adverse effects, has been climbing. Other novel therapeutic agents which aim at signal transduction of osteoclast differentiation and activation are promising as specific inhibitors of bone resorption.