Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) are inflammatory CNS syndromes mainly involving the optic nerve and/or spinal cord and characterized by the presence of serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). The pathology of NMOSD is complicated, while therapies for NMOSD are limited and only partially effective in most cases. This review article focuses on the main pathology of NMOSD involving AQP4-IgG and lymphocyte function. We also review the existing therapeutic methods and potential new treatments. Experimental NMO animal models are crucial for further research into NMO pathology and treatment. However, no AQP4-IgG-immunized animals have been reported. The establishment of NMO models is therefore difficult and primarily depends on the generation of transgenic mice or transcranial manipulation using human or monoclonal mouse anti-AQP4 antibodies. Advantages and disadvantages of each model are discussed.