Despite increases in our understanding of the pathophysiology and environmental and genetic influences of illness in Parkinson's disease, neuroprotection remains an elusive goal. No interventions are widely accepted as disease modifying in Parkinson's disease. Continued research identifying novel therapeutic targets is likely to result in several putative neuroprotective agents. Assimilating lessons from previous neuroprotection trials will be critical in developing future trials aimed at efficiently identifying neuroprotective treatments. Ultimately, overcoming the unique challenges of a heterogenous, slowly progressive disorder with multiple potential outcome measures will be necessary to identify treatments that have meaningful effects.