Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF,RANKL,and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34(IL-34)a novel ligand for c-Fms,plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a,produced by osteoblasts,enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus,recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases. Bone-resorbing osteoclasts are formed from a monocyte / macrophage lineage under the strict control o bone-forming osteoblasts. So far, macrophage colonystimulating factor (M-CSF), receptor activator o nuclear factor-κB ligand (RANKL), and osteoprotegerin Produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF, RANKL, and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34 (IL-34) a novel ligand for c-Fms, plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a, produced by osteoblasts, enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus, recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.