Transcriptome profiling methods are rapidly changing the ways in which insect responses to the environment can be assessed. One article featured in this issue of Molecular Ecology utilizes global expression analysis to extend previous studies examining the basis of insecticide resistance in Helicoverpa species that are devastating crop pests worldwide. In this issue Tao et al. (2012) have used a wide spectrum of biochemical and molecular techniques to examine the extent to which naturally occurring plant compounds and one synthetic insecticide change transcriptome profiles of Helicoverpa armigera larvae (Fig. 1) to enhance their adaptation to plant toxins and insecticides in their diet and environment. With their data highlighting an array of P450 transcripts and a few esterase transcripts that are correlated with increased tolerance to the insecticide deltamethrin, these researchers provide the first comprehensive evaluation of cytochrome P450 monooxygenase (P450), glutathione S-transferase (GST) and esterase (Est) gene responses in a lepidopteran species repeatedly subjected to pyrethroid selection. Building on this information, these researchers venture into the realm of the biorational in showing that RNAi-mediated destruction of one prominent toxin-inducible P450 transcript can increase sensitivity to deltamethrin, thereby compromising larval growth in the presence of this insecticide. The fact that the resulting levels of deltamethrin tolerance in the RNAi-silenced larvae are not restored completely to the levels in larvae whose defences are not stimulated by consuming plant compounds provides further evidence that their adaptive strategies for survival in toxin-rich environments include many different P450, esterase and, possibly, other genes. Together, their data highlight the complexity of the defence systems evolving in lepidopterans and other insect pests.