As populations benefit from increasing lifespans, neurodegenerative diseases have emerged as a critical health concern. How can the fruit fly, Drosophila melanogaster, contribute to curing human diseases of the nervous system? A growing number of neurodegenerative diseases, as well as other human diseases, are being modeled in Drosophila and used as a platform to identify and validate cellular pathways that contribute to neurodegeneration and to identify promising therapeutic targets by using a variety of approaches from screens to target validation. The unique properties and tools available in the Drosophila system, coupled with the fact that testing in vivo has proven highly productive, have accelerated the progress of testing therapeutic strategies in mice and, ultimately, humans. This review highlights selected recent applications to illustrate the use of Drosophila in studying neurodegenerative diseases.