| Parkinson disease (PD) is a complex disorder that encompasses various clinical, epidemiological and genetic subtypes. Approaching PD as a single diagnostic entity has been effective for developing symptomatic therapies but ineffective when targeting neuroprotection or attempting disease modification. The growing number of failed attempts to establish neuroprotective therapies for PD might in part be explained by a simplistic single-target approach to drug development. Here, we argue that more attention should be paid to the symptomatic and pathological differences between patients. We propose that patients belong to distinct nodes or clusters, which are defined by clinical, pathological, genetic and molecular features of the disease. We conclude that the adoption of precision medicine in PD will require a revision of biomarker development efforts, with the ultimate goal of testing putative disease-modifying interventions in well-defined disease subgroups, as opposed to the large and heterogeneous disease populations that are typically recruited into clinical trials.