M-CSF was first characterized as a glycoprotein that induces monocyte and macrophage colony formation from precursors in murine bone marrow cultures. M-CSF binds CD14+ monocytes and promotes the survival/proliferation of peripheral blood monocytes. In addition, M-CSF enhances inducible monocyte functions including phagocytic activity, microbial killing, and cytotoxicity for tumor cells as well as induces the synthesis of inflammatory cytokines such as IL-1, TNFα, and IFNγ in monocytes. Multiple CSF1 mRNA species have been described that arise from alternative splicing in exon 6 and the alternative use of the 3’ end of exons 9 or 10. As a result, two distinct CSF1 protein products are encoded by these transcripts: a cell-surface or membrane-bound form of CSF1 (mCSF1) and a soluble form (sCSF1). Uterine sCSF1 is highly increased during pregnancy. On the contrary, uterine mCSF1 remains low during pregnancy. High levels of M-CSF have been associated to 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. Mouse M-CSF and IL-34 exhibit cross-species specificity, both bind to the human and mouse M-CSF receptors. IL-34 can regulate myeloid development and substitute for CSF-1 in vivo. IL-34 has overlapping but not identical biological activities as M-CSF.