Flies (Diptera) have played a prominent role in human history, and several fly species are reared at different scales and for different beneficial purposes worldwide. Here, we review the historical importance of fly rearing as a foundation for insect rearing science and technology and synthesize information on the uses and rearing diets of more than 50 fly species in the families Asilidae, Calliphoridae, Coelopidae, Drosophilidae, Ephydridae, Muscidae, Sarcophagidae, Stratiomyidae, Syrphidae, Tachinidae, Tephritidae, and Tipulidae. We report more than 10 uses and applications of reared flies to the well-being and progress of humanity. We focus on the fields of animal feed and human food products, pest control and pollination services, medical wound therapy treatments, criminal investigations, and on the development of several branches of biology using flies as model organisms. We highlight the relevance of laboratory-reared Drosophila melanogaster Meigen as a vehicle of great scientific discoveries that have shaped our understanding of many biological systems, including the genetic basis of heredity and of terrible diseases such as cancer. We point out key areas of fly-rearing research such as nutrition, physiology, anatomy/morphology, genetics, genetic pest management, cryopreservation, and ecology. We conclude that fly rearing is an activity with great benefits for human well-being and should be promoted for future advancement in diverse and innovative methods of improving existing and emerging problems to humanity.