Parkinson's disease is a progressive neurodegenerative disorder. At present, only symptomatic treatments are of proven efficacy, whereas strategies that slow or stop the neurodegenerative process are currently not available. The selection of interesting drug candidates or surgical strategies should be based on the soundest clinically driven preclinical validation. My goal here is not to discuss the relative merits of the available models, but to simply raise the issue of the experimental design that has led to the demonstration of efficacy of given compounds in these models. As some compounds previously shown to be active in classic experimental designs fail when tested in clinically relevant experimental designs, I emphasize the need for progressive screening methods and for the use of different animal species before entering into the clinic.