Neurodegenerative illnesses like Alzheimer's, Parkinson's, and ALS are devastating conditions without cures. As populations age, these diseases are rising globally, creating an urgent need for insights into their mechanisms and treatments. The common fruit fly Drosophila melanogaster has emerged as a remarkably versatile model system to study neurodegeneration. With a complex yet accessible nervous system, ease of genetic manipulation, and conserved disease-related genes, the fly provides a powerful platform for dissecting the intricate biology underlying these disorders. This book provides a comprehensive overview of Drosophila neurodegeneration research spanning over four decades. It introduces the genetics and prevalence of major neurodegenerative diseases, along with the advantages of the fly model. Detailed case studies highlight seminal findings from Drosophila models of Alzheimer's, Parkinson's, and ALS diseases. The book explores cellular pathways implicated in neurodegeneration, including protein misfolding, oxidative stress, mitochondrial dysfunction, and neuroinflammation. It discusses techniques for genetic manipulation, behavioral assays, and drug screening in flies. Emerging technologies like CRISPR/Cas9 genome editing are enabling new horizons.