An adequate animal model of a disease should reproduce the cardinal features of its human counterpart. Parkinson’s disease is characterized by akinesia, rigidity, and tremor. Attempts to reproduce Parkinsonian symptoms can be divided in three broad categories according to the method used. Earlier studies were based mostly on destruction of certain brain structures by surgical lesions with or without the help of stereotaxy. Then, with development of our knowledge of neurotransmitters, Parkinsonian features could be reproduced by drugs that affect more or less selectively certain biogenic amines. More recently, the serendipitous discovery of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) provided us with the best model of Parkinson’s disease to date. We will review these models,which have evolved over a period of over fifty years and have provided us with powerful tools to understand the pathophysiology of Parkinson’s disease and to test new therapeutic approaches.