Flystrike is primarily caused by Lucilia cuprina, and it is a major health and welfare issue for at-risk sheep in wool industries. Current control measures commonly involve chemicals such as acaricides which pose challenges like chemical resistance and longer product withholding periods. Other solutions to flystrike, such as vaccination, toxic proteins for use as potential insecticides, Mulesing, and genetic resistance to flystrike, all have specific limitations. To enable more sustainable agriculture practices, it is important to develop technologies that combine targeted effectiveness with a minimal environmental footprint. RNA interference (RNAi) is a eukaryotic process in which transcript expression is reduced in a sequence-specific manner. This makes it a perfect tool for developing efficient and effective biological controls against pests and pathogens. In this chapter, we first describe the life cycle of L. cuprina, the microbial ecology of flystrike development, and the established control methods for L. cuprina management. We subsequently highlight the key advances made in using RNAi technology as a replacement for existing insecticides in agriculture. This discussion includes the challenge, potential solution, and future direction for the development of RNAi-based biocontrol of L. cuprina to improve flystrike management. Moreover, we also describe a research model that enables the evaluation of RNAi efficacy using a L. cuprina larvae feeding bioassay. Together these data suggest that there is a great potential for the application of RNAi to improve the control of L. cuprina for the sustainable management of flystrike.