The fight against pest insects has become a major challenge nowadays to eliminate disease vectors such as malaria, dengue fever or Zika virus, and to grow healthy crops to be able to feed a constantly increasing world population. Insecticides represent one of the main solutions to this challenge but with the introduction of every new insecticide comes inevitably the apparition of resistance a few years later. This chapter provides an overview of the evolution of the different insecticide families over time and their effects on the environment. Resistance mechanisms involving target modification and increased metabolism are detailed for each chemical family. The recent emergence of other resistance mechanisms such as the modification of insect cuticle permeability, the role of ABC transporters in xenobiotic excretion, and the involvement of symbionts are also discussed.