Most tissue macrophages and osteoclasts are regulated by colony-stimulating factor-1 (CSF-1, also known as macrophage CSF). The effects of CSF-1 are mediated by the CSF-1 receptor tyrosine kinase (CSF-1R), through autophosphorylation of CSF-1R and the subsequent phosphorylation of downstream molecules. Triggering this phosphorylation cascade increases gene transcription and protein translation, and induces cytoskeletal remodeling by several signaling pathways, leading to the survival, proliferation and differentiation of target cells. CSF-1-regulated tissue macrophages are important for innate immunity and for tissue development and function. Because CSF-1 regulates the survival, proliferation and chemotaxis of macrophages and supports their activation, this factor is involved in the pathogenesis of several diseases.