Jean-Martin Charcot recorded the best early descriptions of optic neuritis. He reported an account of a woman with multiple sclerosis and feebleness of vision in 1835, illustrating a link between the 2 diseases (DeJong 1970). Sequin published the first American reports of "disseminated cerebrospinal sclerosis," including cases of optic neuritis with subacute transverse myelitis. A more detailed historical description, starting with Arabic texts in the ninth century that began to distinguish between eye paralysis and abnormal perception, is detailed by Volpe (Volpe 2001). Adie, Denny-Brown, and McAlpine all stated that unilateral retrobulbar neuritis was a symptom of multiple sclerosis (Kurtzke 1970). However, many patients with optic neuritis do not develop multiple sclerosis. This suggests there is a spectrum from a sole demyelinating episode, to a forme fruste of multiple sclerosis, to one of many signs of multiple sclerosis. Severe optic neuritis is part of neuromyelitis optica/Devic disease, but the pathogenesis is different from the multiple sclerosis-related idiopathic optic neuritis. This clinical article focuses on optic neuritis as an isolated demyelinating syndrome.