Osteoporosis is one of the most serious under-diagnosed and under-treated recessive diseases, leading to increased mortality and morbidity as well as huge economic burden. The fundamental reason for the occurrence of osteoporosis lies in the disequilibrium between bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. Osteoclast-osteoblast communication plays important roles in the maintenance of hemeostasis. In this review, we present the detailed mechanisms of this communication, including modes of diffusible paracrine factors, cell-cell direct contact and cell-bone matrix interaction. We demonstrate that osteoclasts (or osteoblasts) could not only secrete cytokines, growth factors, chemokines and function in a paracrine manner, but also express molecules on their membranes to bind to the receptors on osteoblasts (or osteoclasts) to transduce bidirectional signals. Moreover, growth factors and cytokines deliberated from bone matrix during bone resorption could also regulate the function of both osteoblasts and osteoclasts. This review gives the latest knowledge of communication factors, some of which are emerging as novel therapeutic targets for future development of antiosteoporotic drugs.