This review presents highlights and updates from of the most significant clinical trials in neuro-ophthalmology to date, the Optic Neuritis Treatment Trial, the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, and the Ischemic Optic Neuropathy Decompression Trial. The quality of evidence for treatment efficacy from these trials and other recent investigations of giant cell arteritis and idiopathic intracranial hypertension is classified herein according to published criteria based on sample size and study design.