Canine GM-CSF (Granulocyte–Macrophage Colony-Stimulating Factor, CSF2) is a hematopoietic cytokine belonging to the colony-stimulating factor family, which also includes G-CSF (CSF3) and M-CSF (CSF1) that regulate the development, proliferation, and activation of myeloid immune cells. In dogs (Canis lupus familiaris), GM-CSF is produced by activated T lymphocytes, macrophages, endothelial cells, fibroblasts, and other stromal cells in response to infection, inflammatory cytokines, or immune stimulation. Canine GM-CSF binds to the GM-CSF receptor (CSF2R) expressed on hematopoietic progenitor cells and mature myeloid cells, activating intracellular signaling pathways such as JAK/STAT, MAPK/ERK, and PI3K–AKT, which promote the proliferation and differentiation of granulocytes, macrophages, and dendritic cells, as well as enhance their functional activity in host defense and antigen presentation. In canine health, GM-CSF contributes to innate and adaptive immune responses during infection and inflammation, particularly through regulation of macrophage and neutrophil activity. Dogs are also valuable comparative animal models for human cancer immunology, and GM-CSF has been studied in canine melanoma models, where GM-CSF–expressing tumor vaccines have been used to stimulate dendritic cell activation and anti-tumor immune responses, providing insights relevant to both veterinary oncology and human cancer immunotherapy.