The voltage-sensitive sodium channel (VSSC) is a critical component of the insect nervous system. Pyrethroids and DDT are insecticides that have been widely used, and they kill insects by perturbations of the VSSC. Decades of insecticide use selected for mutations in Vssc that give rise to resistance in almost all pest insects. However, the mutations responsible for the resistance are not always the same, and some unusual patterns have emerged. This review focuses on what pyrethroid/DDT selection has done, in terms of Vssc changes that have occurred, using four well-studied species as examples of the differences that have evolved. Information is provided about the mutations that occur, potential pathways by which alleles with multiple mutations arose, the relative fitness of the alleles, the levels of resistance conferred, and the geographic distribution of the mutations. The lessons learned and exciting new areas of research are discussed.

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