Aquaporins (AQPs), transmembrane proteins allowing the passage of water and sometimes other small solutes and molecules, are involved in autoimmune diseases including neuromyelitis optica, Sjögren’s syndrome and rheumatoid arthritis. Both autoantibodies against AQPs and altered expression and/or trafficking of AQPs in various tissue cell types as well as inflammatory cells are playing key roles in pathogenesis of autoimmune diseases. Detection of autoantibodies against AQP4 in the central nervous system has paved the way for a deeper understanding in disease pathophysiology as well as enabling diagnosis. This review provides a comprehensive summary of the roles of AQPs in autoimmune diseases.