Recently, the disease-specific neuromyelitis optica (NMO) autoantibody NMO-IgG was detected in the sera of NMO patients, as the specific immunohistochemical pattern of human IgG on mouse brain slices. Aquaporin-4 (AQP4), mainly expressed in astroglial foot processes, was identified as the target for NMO-IgG. For diagnosing NMO, serological tests are mainly performed using a cell-based assay with HEK293 cells transfected with AQP4; this assay has the highest sensitivity (>70%) and specificity (>90%) for diagnosing NMO. However, several assays, such as immunoprecipitation assay, and ELISA systems, for detecting the AQP4 antibody have been reported. Several papers focus on inflammatory and pathological biomarkers, including cytokines, chemokines, and astrocyte markers, for NMO. Pleocytosis in the cerebrospinal fluid (CSF) and an increased CSF IgG: serum IgG/albumin ratio are useful markers of inflammation and blood-brain barrier leakage in NMO patients. Increased concentrations of cytokines such as IL-17, IL-6, and BAFF in the CSF may be key factors that induce the formation of NMO lesions, mainly by promoting the infiltration of neutrophils or plasma cells. Astrocytic damage, reflected by a marked increase in CSF-GFAP levels, was evident in NMO patients, but not in classical multiple sclerosis (MS) patients, indicating that CSF-GFAP is a good marker of lysis during autoimmune astrocytopathy. Therefore, the assessment of such useful biomarkers may become a supportive criterion for diagnosing NMO and NMO spectrum disorders.