Abstract: Challenges in the diagnosis and treatment of Parkinson’s disease: Parkinson’s disease (PD) is an increasingly prevalent neurodegenerative disease, at first sight primarily characterized by motor symptoms, although non-motor symptoms also constitute a major part of the overall phenotype. Clinically, this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost, and the disease progresses inexorably. New biological criteria for PD have been proposed recently and might eventually improve early diagnosis, but they require further validation, and their use will initially be restricted to a research environment (Darweesh et al., 2024). Today, the clinical diagnosis of PD is based primarily on subjective criteria and is impeded by high intra- and interindividual variability. In early disease stages, the differentiation from other diseases can be challenging, hampering the timely selection of the best treatment options. While some of the cardinal motor symptoms associated with PD can be treated effectively in the early stages, disease-modifying interventions and treatments for debilitating non-motor symptoms remain elusive. The many new (primarily pharmacological) strategies currently evaluated for PD are often optimizations of existing approaches (e.g., variations of treatments with dopamine precursors or dopamine receptor agonists) or belong to the class of the highly debated anti-protein aggregation treatments. Breakthrough strategies to reliably halt or slow down PD progression might be just around the corner but the history of unsuccessful translations of promising novel preclinical treatments for PD during the last decades warrants a certain amount of skepticism.