Optic neuritis (ON) is a frequent manifestation of aquaporin-4 (AQP4) antibody-mediated neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disorders, MOGAD). The past few years have seen major advances in the diagnosis and treatment of these two relatively new entities: international diagnostic criteria for NMOSD and MOG-EM have been proposed, improved antibody assays developed, and consensus recommendations on the indications and methodology of serological testing published. Very recently, the results of four phase III trials assessing new treatment options for NMOSD have been presented. With eculizumab, a monoclonal antibody inhibiting complement factor C5, for the first time a relapse-preventing long-term treatment for NMOSD – which has so far mostly been treated off-label with rituximab, azathioprine, and other immunosuppressants – has been approved. Data from recent retrospective studies evaluating treatment responses in MOG-ON suggest that rituximab and other immunosuppressants are effective also in this entity. By contrast, many drugs approved for the treatment of multiple sclerosis (MS) have been found to be either ineffective or to cause disease exacerbation (e.g., interferon-β). Recent studies have shown that not only NMOSD-ON but also MOG-ON usually follows a relapsing course. If left untreated, both disorders can result in severe visual deficiency or blindness, though MOG-ON seems to have a better prognosis overall. Acute attacks are treated with high-dose intravenous methylprednisolone and, in many cases, plasma exchange (PEX) or immunoadsorption (IA). Early use of PEX/IA may prevent persisting visual loss and improve the long-term outcome. Especially MOG-ON has been found to be frequently associated with flare-ups, if steroids are not tapered, and to underlie many cases of “chronic relapsing inflammatory optic neuropathy” (CRION). Both NMOSD-ON and MOG-ON are often associated with simultaneous or consecutive attacks of myelitis and brainstem encephalitis; in contrast to earlier assumptions, supratentorial MRI brain lesions are a common finding and do not preclude the diagnosis. In this article, we review the current knowledge on the clinical presentation, epidemiology, diagnosis, and treatment of these two rare yet important differential diagnoses of both MS-associated ON und idiopathic autoimmune ON.Thieme. All rights reserved.