Huntington's disease is an autosomal dominant neurodegenerative disorder caused by an unstable trinucleotide CAG repeat. The mechanism by which the genetic defect leads to neuronal injury and death is unknown, but is thought to include glutamate-mediated excitotoxicity and abnormalities of mitochondrial energy production. Both of these mechanisms may lead to a final common pathway of increased production of free radical species. Prior clinical trials in patients with Huntington's disease that have addressed these hypotheses have been limited by size. A current, NIH-funded trial of remacemide hydrochloride and Coenzyme Q10 in 340 patients with Huntington's disease is described. This is the largest and longest multi-center trial in Huntington's disease to address the glutamate- and mitochondrial-mediated hypotheses of neurodegeneration.