Bone cells communicate with each other using various cell surface molecules. Membrane-bound ephrin ligands and Eph tyrosine kinase receptors have been characterized in diverse biological processes, including angiogenesis and neuronal development. Several ephrins and Ephs are expressed in osteoclasts and osteoblasts and regulate bone mineral metabolism through bidirectional signaling into not only receptor-expressing cells but also into ligand-expressing cells. We propose that interaction between ephrinB2-expressing osteoclasts and EphB4-expressing osteoblasts facilitates the transition from bone resorption to bone formation during bone remodeling. Other groups have reported the regulation of ephrinB2 by PTH or PTHrP and the possible involvement of EphB4 in osteoarthritis. It is likely that various ephrins and Ephs mediate interaction among bone cells.