The fruit fly, Drosophila melanogaster (Meigen, 1830) has been established as a cornerstone for research into a wide array of subjects including diseases, development, physiology, and genetics. Thanks to an abundance of genetic tools, publicly available fly stocks, and databases, as well as their considerable biological similarity to mammalian systems, Drosophila has been solidified as a key model organism for elucidating many aspects of human disease. Herein is presented an overview of what makes Drosophila such an appealing model organism. In Part I of this chapter, basic Drosophila biology is reviewed and the most relevant genetic tools available to Drosophila researchers are covered. Then in part II, we outline the use of Drosophila as a model organism to study a wide array of pathologies in which Drosophila has been used, along with key advances made in the specific field using the fly as a model organism.