Mosquito-borne diseases, the most well known of which is malaria, are among the leading causes of human deaths worldwide. Vector control is a very important part of the global strategy for management of mosquito-associated diseases, and insecticide application is the most important component in this effort. However, mosquito-borne diseases are now resurgent, largely because of the insecticide resistance that has developed in mosquito vectors and the drug resistance of pathogens. A large number of studies have shown that multiple, complex resistance mechanisms in particular, increased metabolic detoxification of insecticides and decreased sensitivity of the target proteins or genes are likely responsible for insecticide resistance. Gene overexpression and amplification, and mutations in protein-coding-gene regions, have frequently been implicated as well. However, no comprehensive understanding of the resistance mechanisms or regulation involved has yet been developed. This article reviews current knowledge of the molecular mechanisms, genes, gene interactions, and gene regulation governing the development of insecticide resistance in mosquitoes and discusses the potential impact of the latest research findings on the basic and practical aspects of mosquito resistance research.