This book is aimed at generating an updated reservoir of scientific endeavors undertaken to unravel the complicated yet intriguing topic of neurodegeneration. The fruit fly, Drosophila melanogaster has been utilized as a model organism to study a number of human neurodegenerative and neuromuscular diseases for more than two decades. The fruit fly offers multiple advantages for the investigation of the molecular mechanisms of diseases, for instance, short life cycle, high offspring numbers, low cost of maintenance, simple yet powerful genetic manipulation techniques, the availability of mutants, and other genetic tools are only some of the attractive features of Drosophila as a model organism. This book provides greater insight into the classical as well as the recent knowledge obtained from Drosophila that aids to dissect out the molecular mechanisms underlying different neurodegenerative disorders and unravel new scopes for therapeutic interventions. To begin with, readers are acquainted with the different methodologies available to create humanized fly models that faithfully reflects the pathogenicities associated with particular disorders. This book interestingly includes information on the exciting area of neural stem cells. A brief discussion on neurofibrillary tangles, a characteristic phenotype associated with common neurodegenerative disorders, precedes the elaborate description of lessons learned from Drosophila about Alzheimer''s, Parkinson’s, Huntington’s diseases, RNA expansion disorders and Hereditary Spastic Paraplegia Disease. The role played by different signaling pathways on neurodegeneration has been discussed in-depth. The book concludes with the use of Drosophila for identifying pharmacological therapies for neurodegenerative disorders. The wide range of topics covered in this book are relevant not only for beginners who are new to the concept of the extensive utility of Drosophila as a model to study human disorders; but also be a contribution to the scientific community, giving an insight into the paradigm shift in our understanding of neurodegenerative disorders in an interesting and awe-inspiring manner.