This is part of a Spotlight on Neuro-Ophthalmology series for the comprehensive ophthalmologist that emphasizes high-stakes diagnoses and the perils of overdiagnosis. Case-based presentations provide the state-of-the-art approach to common neuro-ophthalmic issues including transient monocular vision loss, temporal arteritis, the swollen optic nerve, ptosis, acute vision loss, and the pediatric patient with neuro-ophthalmic findings. These practical approaches help to ensure no misses and to avoid overdiagnosing and overtesting.