A number of approaches have been taken to recreate and to study the role of genes associated with human neurodegenerative diseases in the model organism Drosophila. These studies encompass the polyglutamine diseases, Parkinson's disease, Alzheimer's disease, and tau-associated pathologies. The findings highlight Drosophila as an important model system in which to study the fundamental pathways influenced by these genes and have led to new insights into aspects of pathogenesis and modifier mechanisms.