Tremendous progress in our understanding of the pathophysiology and clinical manifestations of the prodromal phase of Parkinson disease (PD) offers a unique opportunity to start therapeutic interventions as early as possible to slow or even stop the progression to clinically manifest motor PD. A Parkinson's Prevention Conference, “Planning for Prevention of Parkinson's: A trial design symposium and workshop” was convened to discuss all issues that need to be addressed before the launch of the first PD prevention study. In this review, we summarize the major opportunities and challenges in designing prevention trials in PD, organized by the following critical trial design questions: Who (should be enrolled)? What (to test)? How (to measure prevention)? and the pivotal question, When during the prodromal disease (should we start these trials)? We outline the implications of these questions and their meaning for a responsible, sustainable, and fruitful further planning for prevention trials. Despite the great progress that has been made, it needs to be acknowledged that several queries remain to be carefully considered and addressed because prevention trials are being planned and become a reality.