Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the ‘root’ cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair. However, immunization strategies used to elicit humoral immune responses against aberrant brain proteins have yielded mixed success. While specific proteins can be cleared, the failures in halting disease progression revolve, in measure, around adaptive immune responses that promote autoreactive T cells and, as such, induce a meningoencephalitis, accelerating neurodegeneration. Thus, alternative approaches for protein clearance and neural repair are desired. To this end, our laboratories have sought to transform autoreactive adaptive immune responses into regulatory neuroprotective cells in Parkinson’s disease. In this context, induction of immune responses against modified brain proteins serves to break immunological tolerance, while eliciting adaptive immunity to facilitate neuronal repair. How to harness the immune response in the setting of Parkinson’s disease requires a thorough understanding of the role of immunity in human disease and the ways to modify such immune responses to elicit therapeutic gain. These are discussed in this review.