During 400 million years of existence, insects have rarely succumbed to the evolution of microbial resistance against their potent antimicrobial immune defenses. We found that microbial clearance after infection is extremely fast and that induced antimicrobial activity starts to increase only when most of the bacteria (99.5%) have been removed. Our experiments showed that those bacteria that survived exposure to the insect's constitutive immune response were subsequently more resistant to it. These results imply that induced antimicrobial compounds function primarily to protect the insect against the bacteria that persist within their body, rather than to clear microbial infections. These findings suggest that understanding of the management of antimicrobial peptides in natural systems might inform medical treatment strategies that avoid the risk of drug resistance.