Non-motor symptoms (NMSs) are highly prevalent throughout the course of Parkinson's disease (PD). Pain, autonomic dysfunction and sleep disturbances remain at the forefront of the most common NMSs; their treatment is challenging and their effect on the quality of life of both patients and caregivers detrimental. Yet, the landscape of clinical trials in PD is still dominated by therapeutic strategies seeking to ameliorate motor symptoms; subsequently, effective strategies to successfully treat NMSs remain a huge unmet need. Wider awareness among industry and researchers is thus essential to give rise to development and delivery of high-quality, large-scale clinical trials in enriched populations of patients with PD-related pain, autonomic dysfunction and sleep. In this review, we discuss recent developments in the field of pharmacological treatment strategies designed or re-purposed to target three key NMSs: pain, autonomic dysfunction and sleep disturbances. We focus on emerging evidence from recent clinical trials and outline some exciting and intriguing findings that call for further investigations.