<p>Despite advances in uncovering the immune mechanisms of neurodegeneration in neurodegenerative diseases such as Parkinson's disease (PD) effective therapies that prevent neuronal loss and disease progression remain elusive. Over the past decades, tremendous progress has been made in the field of multiple sclerosis (MS) with a range of disease-modifying therapies (DMTs) being approved. In contrast, available treatment options for PD provide only symptomatic relief, presenting an unmet medical need. Here, we critically review a previously unappreciated dynamic interplay between brain-resident cells and peripheral immune cells in PD versus multiple sclerosis (MS), with a goal to identify shared and unique immunological features. We provide perspectives into the current concepts on the evolution of neuroinflammation in PD, summarize recent findings of immune interventions in PD, and highlight their impact on future design of immune therapies. We propose that deeper understanding of the immunology of PD and further clinical exploration using experiences from therapeutic development in MS could pave the way for the discovery and development of effective DMTs in neurodegeneration.</p>