The discovery of RNAi gene silencing revolutionized our understanding of gene regulation in plants and animals and provided a versatile tool for altering gene expression. In addition to fundamental discoveries, RNAi technology provided a practical tool for applying this approach in biomedicine and agriculture. Here, we will summarize 20 years of development of RNAi technology in spider mites, which led to the first RNAi-based multispecies commercial acaricide. In 2007, the first demonstration that RNAi can functionally silence gene expression in the spider mite Tetranychus urticae used siRNA to silence a developmentally important gene, distal-les. This proof-of-principle of RNAi activity in T. urticae by maternal injection demonstrated dsRNA gene silencing in this species, but it was highly inefficient for the application in pest control. The work of our lab in the past 20 years has tested different methods of RNAi application, explored the machinery of dsRNA processing in T. urticae, identified target tissues with major RNAi effect, and optimized the length of dsRNA, increasing RNAi-based gene silencing to almost 100%. In addition, screening for potential efficient targets for the development of commercial RNAi acaricides revealed sensitive targets that generate rapid mortality in T. urticae. Finally, collaboration with GreenLight Bioscience, a pioneer in the development of RNA-based technology, led to the development and registration of RNAi-based acaricide with multi-species activity against phytophagous spider mites. This work shows that a multidisciplinary approach, combining genomics, transcriptomics, ecology, behavior, and physiology, coupled with technical know-how, is necessary for the development of new technology in pest control. The RNAi acaricides, with zero residues, are compatible with IPM and environmentally safe, representing the new generation of pest control tools with minimal environmental impact.