Resistance to insecticides and herbicides has cost billions of U.S. dollars in the agricultural sector and could result in millions of lives lost to insect-vectored diseases. We mostly continue to use pesticides as if resistance is a temporary issue that will be addressed by commercialization of new pesticides with novel modes of action. However, current evidence suggests that insect and weed evolution may outstrip our ability to replace outmoded chemicals and other control mechanisms. To avoid this outcome, we must address the mix of ecological, genetic, economic, and sociopolitical factors that prevent implementation of sustainable pest management practices. We offer an ambitious proposition.