Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management. The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression. In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.