Insecticides are used globally to control insect pests that impact agriculture, human health and the welfare of domestic pets. The effectiveness of insecticides is diminished by the evolution of insecticide resistance, which often has a metabolic basis. In the literature there is an abundance of references to three phases of metabolism, mediated by metabolic enzymes such as Cytochrome P450s (Phase I) and Glutathione-s-tranferases (Phase II) and efflux proteins such as ABC transporters (Phase III). However there is not a single example of these enzymes and transporters forming a sequential detoxification pathway. At another level there are xenobiotic response pathways where, following induction, over a thousand genes change their levels of expression, but there is little evidence that these pathways are induced by insecticides or provide protection against them. Insect metabolic systems have been shaped for millennia by exposure to environmental toxins but, beyond some oft cited examples (nicotine and pyrethrum), the extent to which these toxins resemble current generation synthetic insecticides is not clear. Therefore we ask whether insecticide exposure is met with a controlled, evolved metabolic response or whether insect metabolism is thrown into chaos? We will discuss our work using genetic and metabolomic approaches to address this question in the model insect, Drosophila melanogaster.