Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) associated with antibodies to aquaporin-4 (AQP4) which has distinct clinical, radiological and pathological features, but also has some overlap with multiple sclerosis and MOG-antibody associated disease. Early recognition of NMOSD is important because of differing responses to both acute and preventive therapy. Magnetic resonance (MR) imaging has proven essential in this process. Key MR imaging clues to the diagnosis of NMOSD are longitudinally extensive lesions of the optic nerve (more than half the length) and spinal cord (3 or more vertebral segments), bilateral optic nerve lesions and lesions of the optic chiasm, area postrema, floor of the IV ventricle, periaqueductal grey matter, hypothalamus and walls of the III ventricle. Other NMOSD specific lesions are denoted by their unique morphology: heterogeneous lesions of the corpus callosum, "cloud-like" Gd-enhancing white matter lesions and "bright spotty" lesions of the spinal cord. Other lesions described in NMOSD, including linear periventricular periependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is yielding further useful information about focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly MR imaging is playing a role in diagnosing seronegative cases of NMOSD.