Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder primarily associated with optic neuritis, myelitis or area postrema syndrome. Several lines of evidence suggest that NMOSD is a humoral immune disease mainly caused by aquaporin-4 antibody and related complement-dependent cytotoxicity against astrocytes. Therefore, NMOSD is distinct from multiple sclerosis (MS). In the diagnosis of NMOSD, it is recommended to examine by high-sensitive cell-based assay targeting against M23-AQP4 but we always have to be careful for the possibility of false negative or false positive result due to each assay. To prevent relapse of the disease, it is best to avoid disease-modifying drugs used for treatment of MS because of possible acute exacerbation of the disease activity. Usually, it is recommended to start treatment with administration of oral steroids and then gradually move to immunosuppressants. However, side effects of such treatments need to be evaluated. Currently, there are additional options for therapy with biopharmaceutical agents such as eculizumab, satralizumab, rituximab, or inebilizumab to prevent relapse of the disease. These new options can clearly exceed or surpass the usual treatments and should be considered positively in aggressive cases of NMOSD.