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In this chapter, a review of the novel nonsteroidal diacylhydrazine insecticidal chemistries is given, which are true agonists of the steroidal insect molting hormone, 20-hydroxyecdysone (ecdysterone), but selectively active against only lepidopteran and/or coleopteran larvae. The chemical synthesis for the five compounds and the structure-activity work are described that went into discovering at least three of the five compounds (methoxyfenozide, tebufenozide, and halofenozide). In this context, the current understanding of the physiological, biochemical, and molecular basis of the selective mode of action of these insecticidal chemistries is also included. The detailed biological (both lethal and sublethal) effects of the five compounds on the intoxicated pest developmental stages are described. The commercial application of the registered diacylhydrazine active ingredient containing insecticides has been reviewed. Finally, the safety of these diacylhydrazine insecticides, their toxicological, environmental fate and residue, and resistance and resistance management aspects have also been evaluated.