The avermectins represent a group of natural compounds with potent pesticidal activities. Because of their novel mode of action, they represent an important resource for pest control and resistance management. In the Colorado potato beetle, the house fly, and the two-spotted spider mite, resistance to abamectin is usually autosomal, recessive, and polygenic. Although these aspects are beneficial in resistance management, the fact that resistance could be readily selected for suggests that abamectin needs to be used in moderation. Furthermore, several major resistance mechanisms (e.g. excretion, oxidative metabolism, penetration) and minor factors (e.g. altered target site, conjugation, hydrolysis/sequestration) have been implicated in abamectin resistance. Thus, the question is not whether resistance to abamectin will occur but is simply when and how it will occur. To address this problem, we have gathered information on the genetics, biochemical mechanisms, effectiveness of synergists, and cross-resistances to other insecticides from three abamectin-resistant insects. Judicious implementation of this information may prove useful in the resistance management of this natural pesticide.