This chapter provides an overview of autoimmune polyendocrine syndromes (APSs) in humans and discusses the potential existence of APSs in dogs. APSs are a group of clinical conditions characterized by the failure of multiple endocrine glands, often occurring sequentially over many years. The genetic susceptibility, clinical features, diagnosis, and treatment of APSs in humans are discussed, as well as the controversies surrounding the existence of APSs in dogs. The clinical features, diagnosis and treatment of potential APSs in dogs are outlined. Guidance on hormone replacement and immunosuppression therapy is provided. Overall, the prognosis for dogs with combined endocrine deficiencies is generally favourable with appropriate treatment.