Bidirectional Eph-Ephrin signaling as a focal point of research in cell-cell communications is critical for generation of nerves and vesssels as well as invation and metastasis of tumor cells. The roles for Ephrin-Eph bidirectional signaling in bone remodeling were important. EphrinB2 is expressed on osteoblasts and EphB4 is expressed on osteoclasts. Forward signaling through the EphB4 receptor into mesenchymal precursors promotes osteoblast differentiation, while reverse signaling through the EphrinB2 ligand into osteoclast suppresses differentiation. Signaling between the ligand EphrinB2 and the receptors EphB4 explains bidirectional signaling between osteoblasts and osteoclasts,bone absorption and remodeling, which may lay a theoretical foundation for identifying drug targeting and preventing and treating bone loss.