This review describes the development of a new integrated approach to the generation of a novel type of insect neuropeptide (Np) antagonists and putative insect control agents based on conformationally constrained compounds. The new approach, termed insect Np-based antagonist insecticide (INAI), was applied to the insect pyrokinin (PK)/pheromone biosynthesis-activating Np (PBAN) family as a model and led to the discovery of a potent linear lead antagonist and several highly potent, metabolically stable backbone cyclic (BBC) conformationally constrained antagonists that were devoid of agonistic activity and inhibited sex pheromone biosynthesis in female moths in vivo. This review summarizes the above approach, briefly describes the PK/PBAN Np family, presents data on the in vivo activity of the antagonists, summarizes data on the PK/PBAN receptor, and introduces the advantages of this method for generation of Np antagonists as a basis for the design of insect control agents.