Neuromyelitis optica (NMO) is an inflammatory neurologic disease clinically characterized by severe optic neuritis (ON) and transverse myelitis (TM). The relationship between NMO and multiple sclerosis (MS) has long been a matter of debate. However, the discovery of an NMO-specific autoantibody, NMO-immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our understanding of the disease, and the clinical, magnetic resonance imaging (MRI), optical coherence tomography, and laboratory examinations have clarified unique features of NMO that are distinct from MS. The term NMO spectrum disorders (NMOSD) incorporating spatially limited forms was introduced, as patients with recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM (LETM) alone are also often AQP4 antibody-seropositive. Moreover, studies of seropositive cases have shown that more than half of them have brain lesions, some of which are unique to NMO, and can be the onset manifestation. Some clinical features of AQP4 antibody-seronegative NMO differ from seropositive, but it remains unknown whether they are pathologically distinct. Immunosuppressive treatments are effective for acute attacks and prevention of relapses of NMOSD, and new molecularly targeted drugs are under investigation. Importantly, some disease modifying drugs for MS may exacerbate NMOSD, making early differential diagnosis of the two diseases crucial. We review the evolving clinical spectrum, the updated clinical, MRI, neuro-ophthalmological and laboratory findings, and the current status of treatment in NMOSD.