The Optic Neuritis Treatment Trial previously reported that corticosteroids accelerated visual recovery in optic neuritis (ON) without improving outcome. This finding related largely to multiple sclerosis (MS), and subsequently neurologists tended to await spontaneous recovery in ON. Since then, non-MS cases of ON have been identified with antibodies to aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG). These disorders can closely mimic multiple sclerosis-associated or idiopathic demyelinating optic neuritis (MS/IDON) initially but risk a worse visual outcome. Scrutinising the clinical features and neuroimaging often enables differentiation between MS/IDON and other causes of ON. Early treatment with high-dose corticosteroids is an important determinant of visual outcome in non-MS/IDON. Prompt use of plasma exchange may also save sight. In this review, we contrast the presentations of myelin oligodendrocyte glycoprotein associated optic neuritis (MOG-ON) and aquaporin 4 associated optic neuritis (AQP4-ON) with MS/IDON and provide an approach to acute management while awaiting results of antibody testing.