Parkinson's disease (PD) is the most common neurodegenerative movement disorder. While the classic clinical-neuropathological features of PD have been well established, mechanisms underlying brain degeneration in PD are unknown, and only partially effective symptomatic treatments for PD exist. Further, there are no therapeutic interventions that prevent PD or block the progression of this relentless neurodegenerative disorder. However, dramatic new insights into the role of alpha-synuclein (AS) in the pathobiology of PD have emerged recently, and this has led to the development of transgenic animal models of PD-like AS pathologies. Continuing advances in this research direction should advance understanding of PD and accelerate discovery of more effective therapies for this and related synucleinopathies.