Animal models play a critical role in our understanding of the cause of human diseases and provide an opportunity to evaluate new therapeutic treatments. The usefulness of an animal model is dependent, in part, on how closely it resembles neurochemical, neuropathologic, and behavioral features of the human condition. Other considerations that may enhance the value of a model include expense, availability, reproducibility, animal morbidity and mortality, and investigator experience. Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by slow movements, tremor, and walking impairment due to loss of midbrain nigrostriatal neurons and depletion of striatal dopamine. In the PD research field, a number of neurotoxic, pharmacologic, and transgenic animal models are available for research studies. We will focus on the advantages and disadvantages of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse and nonhuman primate models of PD. Our goal is to guide researchers in the appropriateness of the MPTP models in their studies by balancing understanding of the models, objectives of the study, and health and safety of the animals. In addition, the technical use and safe handling of MPTP are discussed.