The crosstalk of the immune and central nervous systems (CNS) plays a major role in the progression of neuroinflammation in the context of Parkinson’s disease (PD), which is characterized by a slow and progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Alpha-synuclein (α-syn) is the main component of the classic neuronal Lewy body that develops during the course of the disease. Recently, studies from patient samples have shown alterations in markers of inflammation and immune cell populations, which have the capacity to initiate and exacerbate neuroinflammation and perpetuate the neurodegenerative process. This chapter presents evidence for the bidirectional communication between the brain and the immune system in PD and discusses the opportunities to glean from the emerging immunological evidence to develop effective alternative treatments for the disease.