Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune central nervous system disease with low incidence and involving spinal cord and optic nerve. The clinical manifestations of NMOSD are various, thus，it needs to distinguish from different diseases and poses challenges on diagnosis and differential diagnosis. This paper discusses the diagnosis and imaging differential diagnosis of NMOSD, focusing on the neuroimaging features, in order to improve the clinicians’ understanding of NMOSD and other related diseases, and improve the abilities of diagnosis and differential diagnosis.