This paper describes an overview of recent insights concerning some socially relevant neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and Creutzfeldt-Jakob's (CJD) diseases, amyotrophic lateral sclerosis (ALS) and epilepsy. For each pathological state, the direct and/or indirect involvement of P-glycoprotein (P-gp) efflux transport is underlined. On this basis, P-gp still represents an innovative target which can offer new tools for the development of more effective and preventive therapeutic strategies for neurodegenerative disorders. For each of them, therefore, a possible use of drugs affecting P-gp transport activity has been suggested.