This chapter addresses painful optic neuritis (PON) through the lens of a representative case of a 25-year-old woman who presented with acute unilateral vision loss and retro-orbital pain exacerbated by eye movement. The hallmark clinical presentation—pain preceding visual deficits—illustrates the characteristic temporal profile of inflammatory optic neuropathy. The increased T2-weighted signal intensity in the posterior intraorbital segment of the left optic nerve supports the diagnosis. The patient was treated with high-dose intravenous methylprednisolone to speed up recovery. This case exemplifies a clinically isolated syndrome (CIS) without evidence of multiple sclerosis, neuromyelitis optica, or myelin oligodendrocyte glycoprotein (MOG) antibody disease based on cerebrospinal fluid (CSF) analysis, neuroimaging, and serological testing. The chapter outlines current diagnostic criteria from the International Classification of Headache Disorders, third edition (ICHD-3), and evidence-based management approaches. Key clinical pearls include recognizing pain with eye movement as a pathognomonic sign, understanding the differential diagnosis between typical and atypical optic neuritis, and the importance of comprehensive neuroimaging and serological testing in risk stratification. Management guidelines emphasize the role of early corticosteroid therapy, indications for plasma exchange in severe cases, and criteria for initiating disease-modifying treatments in patients at high risk for developing chronic demyelinating disorders. The growing importance of biomarkers (aquaporin-4 [AQP4] and MOG antibodies) in identifying distinct phenotypes with different prognostic implications is highlighted as central to modern clinical practice.