Publisher Summary Animal models are an essential tool to study human diseases, not only to enable a thorough investigation into the mechanisms involved in the pathogenesis of a disease but also to help in the development of therapeutic strategies. This chapter describes genetic as well as pharmacological manipulations used to develop animal models that mimic Parkinson's disease (PD) and discuss the advantages and disadvantages of the various models. PD is a basal ganglia-related movement disorder characterized by tremor, rigidity or stiffness of movement, and bradykinesia or slowness of movement. It is a late-onset, progressive, neurodegenerative disease involving the degeneration of the nigrostriatal pathway and dopaminergic neurons of substantia nigra. Like reserpine, methamphetamine (METH) administration results in dopamine depletion at the level of dopaminergic nerve terminals with minimal effect in the nigral cell bodies. The METH model is an acute model of striatal dopamine depletion. The 6-hydroxydopamine (6-OHDA) model does not mimic all the clinical and pathological features characteristic of PD.