Animal models have long served as indispensable systems for exploring how human diseases arise and progress. These organisms span a wide biological range—from Caenorhabditis elegans to non-human primates—and have enabled discoveries that would otherwise remain unattainable. Their usefulness is typically linked to the degree of genetic and physiological similarity they share with humans, making it possible to generalize many research findings. Yet such translational assumptions are not always accurate. Among current model organisms, Drosophila melanogaster has gained significant traction for dissecting the biochemical foundations of numerous human disorders. Its short life cycle, high reproductive rate, simple genome with reduced genetic redundancy compared with vertebrate systems, and the extensive availability of genetic manipulation tools have collectively strengthened its reputation as a powerful disease model. This review outlines the contributions of various animal models to biomedical investigations, with particular emphasis on the fruit fly’s role in elucidating biochemical mechanisms underlying persistent human diseases.