Ovine/Caprine Macrophage Colony-Stimulating Factor (M-CSF) is a cytokine that regulates the development, proliferation, and survival of monocytes and macrophages in sheep (Ovis aries) and goats (Capra hircus). The M-CSF protein is identical at the amino acid level in these two species, reflecting strong evolutionary conservation of this key regulator of macrophage biology in small ruminants. M-CSF is produced by several cell types, including fibroblasts, endothelial cells, epithelial cells, and stromal cells, in response to tissue signals and inflammatory stimuli. Ovine and caprine M-CSF bind to the colony-stimulating factor-1 receptor (CSF1R), a receptor tyrosine kinase expressed on monocytes and macrophage lineage cells, activating intracellular signaling pathways such as PI3K–AKT, ERK/MAPK, and JAK–STAT that promote differentiation and maintenance of macrophage populations. Through these mechanisms, M-CSF supports macrophage-mediated immune surveillance, phagocytosis, tissue homeostasis, and inflammatory responses. Because macrophages play a central role in host defense, M-CSF–mediated macrophage function is important for maintaining immune health and resistance to infection in sheep and goats. In cell culture, recombinant ovine/caprine M-CSF is commonly used to promote differentiation of monocytes into macrophages and to support macrophage proliferation and functional assays in vitro. Ovine and caprine M-CSF are also studied in veterinary and animal model research, including investigations of macrophage responses to important livestock pathogens such as Mycobacterium avium subsp. paratuberculosis, Brucella spp., and small ruminant lentiviruses.