Simple SummaryWithin the fly family (Diptera), various species transmit diseases to humans and farm animals or are pests of many crop plants. Most species of flies, however, play key ecological roles in sustaining life on Earth, and several species are reared at different scales and for various beneficial purposes worldwide. Here, we review the special place of fly rearing in relation to the tremendous role that Diptera rearing technology has contributed to the development of our state of knowledge of genetics, sterile insect technique (SIT), biological control, and quality control. We summarize information on the rearing of flies in the fields of the animal feed and human food industries, pollination services, pest control, medical wound therapy treatments, criminal investigations, and as model organisms for the development of several biological and medical fields. We document the importance of fly rearing technology as a basis for many other rearing systems approaches, making the history of Diptera rearing as a launching point for most other insect rearing systems.AbstractFlies (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-rearedDrosophila melanogasterMeigen 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.