Despite many pharmacological and surgical treatments addressing the symptoms of Parkinson’s disease, there are no approved treatments that slow disease progression. Genetic discoveries in the last 20 years have increased our understanding of the molecular contributors to Parkinson’s pathophysiology, uncovered many druggable targets and pathways, and increased investment in treatments that might slow or stop the disease process. Longitudinal, observational studies are dissecting Parkinson’s disease heterogeneity and illuminating the importance of molecularly defined subtypes more likely to respond to targeted interventions. Indeed, clinical and pathological differences seen within and across carriers of PD-associated gene mutations suggest the existence of greater biological complexity than previously appreciated and increase the likelihood that targeted interventions based on molecular characteristics will be beneficial. This article offers our current perspective on the promise and current challenges in subtype identification and precision medicine approaches in Parkinson’s disease.