According to the pre-adaptation hypothesis, the evolution of insecticide resistance in plant-eating insects co-opts adaptations that initially evolved during chemical warfare with their host plants. Here, we used comparative statistics to test two predictions of this hypothesis: (i) Insects with more diverse diets should evolve resistance to more diverse insecticides. (ii) Feeding on host plants with strong or diverse qualitative chemical defenses should prime an insect lineage to evolve insecticide resistance. Both predictions are supported by our tests. What makes this especially noteworthy is that differences in the diets of plant-eating insect species are typically ignored by the population genetic models we use to make predictions about insecticide resistance evolution. Those models surely capture some of the differences between host-use generalists and specialists, for example, differences in population size and migration rates into treated fields, but they miss other potentially important differences, for example, differences in metabolic diversity and gene expression plasticity. Ignoring these differences could be costly.