A 20-year-old otherwise healthy male, with a known family history of Leber hereditary optic neuropathy (LHON) presents with acute visual loss in one eye. He is accompanied at his appointment by his elder brother who lost vision in both eyes 3 years earlier and by his sister who is asymptomatic. They all ask you what can possibly be done. The past two decades have witnessed remarkable advances in our understanding of the clinical presentation, genetics and even the pathophysiology of LHON, a maternally inherited cause of usually blinding bilateral visual loss caused by point mutations in the mitochondrial DNA (Newman, 2005; Yu-Wai-Man et al ., 2009, 2011; Fraser et al ., 2010). However, investigations into potential therapies for LHON and other mitochondrial disorders are still in their nascency. In this issue of Brain , Klopstock et al. (2011) report on the first randomized placebo-controlled treatment trial of any agent in patients with LHON. This trial also represents one of the first adequately powered randomized controlled treatment trials for any mitochondrial DNA disease. In most patients with LHON, visual loss is devastating and permanent, with acuities typically worse than 20/200 in both eyes (Newman, 2005; Yu-Wai-Man et al ., 2009, 2011; Fraser et al ., 2010). Approximately 50% of patients with visual loss from LHON will experience sequential eye symptoms, with intervals between affected eyes ranging from days to months, but typically at an interval of 2–4 months (Newman et al ., 1991; Riordan-Eva et al ., 1995). At least 97% of patients with visual loss in one eye will have the second eye involved within 1 year (Newman et al. , 2005). In some patients, visual recovery may occur after acute visual loss, sometimes manifested as a ‘fenestration’ within a visual field defect …