Existing therapeutic strategies for managing Parkinson disease (PD), which focus on addressing the loss of dopamine and dopaminergic function linked with degeneration of dopaminergic neurons, are limited by side effects and lack of long-term efficacy. In recent decades, research into PD pathophysiology and pharmacology has focused on understanding and tackling the neurodegenerative processes and symptomology of PD. In this Review, we discuss the challenges associated with the development of novel therapies for PD, highlighting emerging agents that aim to target cell death, as well as new targets offering a symptomatic approach to managing features and progression of the disease.