Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially in mice, has aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of exhibiting a broad range of phenotypes and coupled with their conserved genetic and anatomical structures provides unparalleled molecular and pathological tool to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. α-Synuclein preformed fibril (PFF) injections, which induce the aggregation of endogenous α-synuclein, remarkably recapitulate pathological processes observed in human PD. Here, we provide an overview of the generation and characterization of transgenic and knockout mice and the α-synuclein PFF models used to study PD followed by molecular insights that have been gleamed these PD mouse models.