I read with interest the study by Hacker et al.,1 which builds on experience by the same group over the past several years.2–4 Although there are reasonable preclinical data and proposed mechanisms for subthalamic nucleus (STN) deep brain stimulation (DBS)-mediated neuroprotection5—as well as a clinical signal from the Vanderbilt cohort4—the issue of disease modification has to be approached with extreme caution and is not synonymous to isolated symptom control. Any such prospective clinical trial—perhaps even with a delayed start design—would have to collect thoroughly motor, nonmotor, quality of life, and ideally potential biomarker data. Certainly, the Vanderbilt group has thoughtfully considered employing STN DBS early enough to assess for disease progression, yet the present study showed no other improvements in any of their outcome data—as noted by Fasano and Bhowmick6—except for ON-medication tremor. I also wonder why the OFF-medication tremor scores were not published. Reduction of dyskinesia and polypharmacy were expected in this study probably because of better tremor control on DBS. Eventually, their planned multicenter, phase III study would have to demonstrate an acceptable safety profile, a clinically relevant magnitude of disease modification, and acceptable financial and other costs to healthcare systems to lead to a change in current practice.