Acute demyelinating optic neuritis associated with multiple sclerosis (MS) is the most common cause of inflammation of the optic nerve. The Optic Neuritis Treatment Trial (ONTT) has provided important clinical data on the use of corticosteroids, and demonstrated that patients with characteristic inflammatory lesions within the brain on magnetic resonance imaging had a greater chance of developing clinically definite MS (CDMS). The current approach to patients with optic neuritis has been modified by the results of the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS). Patients with an initial clinical episode of demyelination (optic neuritis, incomplete transverse myelitis, or brain-stem/cerebellar syndrome) and at least two characteristic demyelinating lesions within the brain were randomized to receive interferon beta-1a or placebo after initial treatment with intravenous corticosteroids. At the 3-year point patients treated with interferon beta-1a showed a 50% less risk of CDMS. The results of this study have set the standard for patients with a first bout of demyelinating optic neuritis.