Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies, have all something in common. They all belong to a group of neurodegenerative diseases called synucleinopathies, including preclinical Parkinson, characterized by the abnormal accumulation of aggregates of α-synuclein protein in neurons, nerve fibres or glial cells. Current evidence points to misfolded α-synuclein protein as the causative agent of the development and progression of these diseases. To date, treatments for these conditions are inexistent and research is ongoing to find new therapies. Vaccines are one of the prime potential treatments being investigated because it is broadly applicable, requires infrequent administration and maintains low production costs for treating a large population. This last decade has seen significant progress in active immunization against α-synuclein, both in preclinical animal models and early clinical development. This review presents some preclinical animal models for synuclein and Parkinson and highlights their progress in translation to the clinical setting. It also discusses current clinical applications, stressing different approaches taken to address α-synuclein pathology and addresses the challenges, trends, and future perspectives of current vaccination programs. Syncrosome, a French preclinical CRO, is currently developing this alpha-synuclein model to look at neuroprotection, it will add to its pool of other different Parkinson’s disease animal models which include the 6-OHDA model (late and early stage preclinical disease model) and the Haloperidol model used for rapid screenings.