M-CSF was first characterized as a glycoprotein that induces monocyte and macrophage colony formation from precursors in murine bone marrow cultures. M-CSF is constitutively present at biologically active concentrations in human serum. It binds CD14+ monocytes and promotes the survival/proliferation of human peripheral blood monocytes. In addition, M-CSF enhances inducible monocyte functions including phagocytic activity, microbial killing, cytotoxicity for tumor cells as well as synthesis of inflammatory cytokines such as IL-1, TNF-α, and IFN-γ in monocytes. M-CSF induces RANKL production in mature human osteoclasts; consequently, M-CSF is a potent stimulator of mature osteoclast resorbing activity. Also, M-CSF induces VEGF in monocytes in human tumors. High levels of M-CSF, mononuclear phagocytes, and VEGF are associated with poor prognosis in patients with cancer. High levels of M-CSF have been associated with different pathologies such as pulmonary fibrosis and atherosclerosis. M-CSF binds to its receptor M-CSFR, and this receptor is shared by a second ligand, IL-34. Human M-CSF and IL-34 exhibit cross-species specificity, both bind to human and mouse M-CSF receptors.