Monoclonal antibodies are emerging as advanced therapies in companion-animal medicine, with approved or clinically evaluated applications in canine and feline osteoarthritis pain, canine atopic dermatitis, and selected infectious-disease and oncological settings. This critical narrative review integrates peer-reviewed studies, regulatory records, product information, and publicly available therapeutic-antibody sequence resources to examine target biology, species adaptation, Fc function, developability, and clinical implementation. Anti-NGF and anti-IL-31 products demonstrate the clinical value of long dosing intervals, whereas oncology and infectious-disease programmes remain subject to indication-specific efficacy and safety requirements. Canine and feline IgG subclasses, Fc-receptor and FcRn biology, incomplete feline framework resources, manufacturing economics, and owner-funded care all influence candidate design and deployment. Emerging bispecific antibodies, antibody–drug conjugates, VHHs, mRNA-based approaches, and AI-assisted strategies are most relevant when they address a defined veterinary use case. We propose a translational framework linking target validation, species-adapted engineering, species-matched assays, manufacturability, regulatory evidence, and real-world deployment.