Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system characterized by the involvement of the optic nerve and spinal cord. The main clinical features are optic neuritis, acute myelitis, and area postrema syndrome. Aquaporin-4 (AQP4)-IgG-positive patients accounted for the majority and compared with AQP4-IgG-negative patients, the clinical symptoms were more severe, the recurrence was more frequent, and the disability rate was higher. The pathogenesis of AQP4-IgG-positive NMOSD is still not clear. This article reviews the research progress of the pathogenesis of AQP4-IgG-positive NMOSD.