The past ten years have seen the elucidation of the molecular basis of insect resistance to many chemical insecticides. Target genes, mostly in the nervous system, have been identified and cloned from Drosophila melanogaster and resistance-associated mutations have been examined in a range of pest insects. More recently, with the advent of annotated insect genomes, resistance mediated by complex multi-gene enzyme systems such as esterases, cytochrome p450s and glutathione-S-transferases has also been elucidated. In this article, we review the impact of Drosophila genetics on the field of insect resistance and focus on the current and future impact of genomics. These studies enable us to address three fundamental questions in the evolution of resistance. How many genes are involved? How many mutations are there within these genes? How often do these mutations arise in natural populations?