Over the past 13 years neuromyelitis optica spectrum disorder (NMOSD) has emerged as a discrete form of demyelinating disease of the central nervous system in which antibodies against a water channel found in high concentration on astrocytes are frequently found. Following the discovery of this pathogenic antibody the phenotype of this condition, previously known as Devic’s disease, has broadened from one of monophasic or recurrent, optic neuritis and transverse myelitis, to include area postrema lesions, hypothalamic lesions and a fulminant encephalopathic presentation. Clues to the diagnosis include clinical presentations related to the above locations of pathology and imaging changes including longitudinally extensive spinal cord lesions, extensive optic nerve lesions, particularly lesions posterior to or involving the chiasm, and reactive cerebrospinal fluid. Early identification of this disorder is important as the prognosis without treatment is poor and generally worse than is seen in multiple sclerosis (MS). In addition, the approach to treatment (immunosuppression and anti-B-cell therapy) is different to MS and there is a concern that some disease modifying therapies that are helpful in MS may be harmful in NMOSD.