Despite great advances in clinical diagnostics, genetics and molecular biology, neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD) still pose great challenges, both in terms of understanding their pathophysiology as well as their treatment. Organisms able to adequately model the intricacies of the disease mechanism and respose to potential treatment, whilst not compromising on ease of handling, studying and manipulating in order to study them, represent the holy grail of translational biology and medicine. Here, we review the suitability of the fruit fly, Drosophila melanogaster, as a model organism in the field of neurodegeneration. We briefly summarize the history of scientific research concerning this organism, review the molecular, genetic and pharmacological toolbox available and we discuss the ways this toolbox has been applied to research in neurodegeneration. Finally, by reviewing some findings in the fruit fly which were subsequently translated to and validated in other organisms on their way to the clinic, the power and robustness of Drosophila melanogaster is highlighted.