Abstract: The discovery of neonicotinoids as important novel insecticides represents a milestone in insecticide research over the past two decades. Both nicotinoid and neonicotinoid insecticides act on the insect central nervous system as agonists of the postsynaptic nicotinic acetylcholine receptors (nAChRs) but in a different way,the neonicotinoid insecticides exhibit high selective toxicity to insects.The molecular mechanisms for selective action of neonicotinoid insecticides based on the structure-activity relationships,molecular feature of nicotinoids and neonicotinoids,and their binding site and subsite specificity were expounded.