Optic neuritis (ON) is an inflammatory optic neuropathy that is often a harbinger of central nervous system (CNS) demyelinating disorders. ON is frequently misdiagnosed in the clinical arena, leading to either inappropriate management or diagnostic delays. As a result, patients may fail to achieve optimal recovery. The treatment response to corticosteroids and long term risk of multiple sclerosis was established in the first clinical trials conducted roughly 30 years ago. Spontaneous resolution was observed in the vast majority of patients and intravenous high-dose corticosteroids hastened recovery; half of the patients eventually developed multiple sclerosis. Over the ensuing decades, the number of inflammatory conditions associated with ON has significantly expanded exposing substantial variability in the prognosis, treatment, and management of ON patients. ON subtypes can frequently be distinguished by distinct clinical, serological, and radiological profiles allowing expedited and specialized treatment. Guided by an increased understanding of the immunopathology underlying optic nerve and associated CNS injuries, novel disease management strategies are emerging to minimize vision loss, improve long-term surveillance strategies, and minimize CNS injury and disability. Knowledge regarding the clinical signs and symptoms of different ON subtypes is essential to guide acute therapy, prognosticate recovery, accurately identify underlying CNS inflammatory disorders, and facilitate study design for the next generation of clinical and translational trials.