Canine Leukemia Inhibitory Factor (LIF) is a multifunctional cytokine belonging to the IL-6 family—which includes IL-6, IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), and IL-27—all of which signal through receptor complexes containing the shared gp130 subunit. In dogs (Canis lupus familiaris), LIF binds to the LIF receptor (LIFR) in association with gp130, activating JAK/STAT3, MAPK, and PI3K signaling pathways that regulate cell survival, differentiation, immune modulation, and tissue repair. Canine LIF plays important roles in reproductive biology, particularly in endometrial receptivity and embryo implantation, as well as in hematopoiesis and neural cell survival. In canine health, LIF-mediated STAT3 signaling is relevant in inflammatory diseases, tissue regeneration, and oncology, where dysregulated LIF expression may contribute to tumor progression, tumor microenvironment remodeling, or fibrosis in cancers such as lymphoma, mammary tumors, and osteosarcoma. LIF may also influence immune balance during chronic inflammatory conditions such as inflammatory bowel disease. As both a regenerative and immunomodulatory cytokine, canine LIF is important in studies of fertility, stem cell biology, cancer pathogenesis, and cytokine network regulation. Given the dog’s role as a spontaneous model for human cancer and chronic inflammatory disease, characterization of canine LIF supports translational research into IL-6 family signaling and development of targeted STAT3-modulating therapies relevant to both veterinary and human medicine.