Polyglutamine (polyQ) diseases are a family of dominantly transmitted neurodegenerative disorders caused by an abnormal expansion of CAG trinucleotide repeats in the protein-coding regions of the respective disease-causing genes. Despite their simple genetic basis, the etiology of these diseases is far from clear. Over the past two decades, Drosophila has proven to be successful in modeling this family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. Additionally, it has been valuable in probing the pathogenic mechanisms, in identifying and evaluating disease modifiers, and in helping elucidate the normal functions of disease-causing genes. Knowledge learned from this simple invertebrate organism has had a large impact on our understanding of these devastating brain diseases.