The abnormal accumulations of fibrillar α-synuclein in Lewy bodies and the mutations in the gene for α-synuclein in familial forms of Parkinson's disease have led to the belief that this protein has a central role in a group of neurodegenerative diseases known as the synucleinopathies. Our understanding of the biology of α-synuclein has increased significantly since its discovery in 1997, and recently developed animal models of the synucleinopathies have contributed to this understanding. The information gleaned from animal models has the potential to provide a framework for continuing the development of rational therapeutic strategies.