Abstract: Diamide insecticides are used to control a variety of destructive agricultural Lepidopteran and Coleopteran pests. They possess a novel mechanism of action and are safe for nontarget organisms; thus, they have become among the best-selling insecticides in the world. Mutations recently discovered in resistant insect populations significantly reduce their efficacy, causing enormous economic losses to agricultural production in various countries. The molecular target of diamide insecticides, the ryanodine receptor (RyR), has been widely studied as a new hot target and has received much attention in recent years. The latest findings on the structure and function of insect RyRs, including 1) the binding site and mode of action of diamide insecticides, 2) the impacts of resistance mutations on the structure and function of RyRs, 3) potential new target sites on RyRs other than the diamide insecticides binding site, and 4) structural differences of the classic and new target sites between the target and nontarget organisms, were summarized in the review. Finally, how the progress in RyR structural biology might facilitate the design and development of a new generation of green pesticides was also discussed.