In 1987, the DATATOP clinical trial was initiated to examine the benefits of deprenyl (selegiline) and alpha-tocopherol in slowing the progression of Parkinson's disease (PD). After 14 +/- 6 (mean +/- SD) months of controlled observation, deprenyl 10 mg/day was found to significantly delay the time until enough disability developed to warrant the initiation of levodopa therapy. This effect was largely sustained during the overall 8.2 years of observation, including open-label deprenyl treatment and a second treatment randomization to continue deprenyl or switch to placebo. There were no accompanying benefits of deprenyl in postponing levodopa-related adverse effects or extending life. Alpha-tocopherol produced no benefits. The 2.1% per year mortality rate of the DATATOP cohort was remarkably low, about the same as an age-matched population without PD. Neuroprotective therapy remains an elusive goal for the experimental therapeutics of PD. Advances in understanding pathogenesis, a robust pipeline of rational treatments, and the advent of valid and reliable biologic markers hold promise in the coming decade for developing and achieving neuroprotective therapies for PD.