As the malaria burden persists in most parts of the developing world, the concept of implementation of new strategies such as the use of genetically modified mosquitoes to control the disease continues to gain support. In Africa, which suffers most from malaria, mosquito vector populations are spread almost throughout the entire continent, and the parasite reservoir is big and continuously increasing. Moreover, malaria is transmitted by many species of anophelines with specific seasonal and geographical patterns. Therefore, a well designed, evolutionarily robust and publicly accepted plan aiming at population reduction or replacement is required. The task is twofold: to engineer mosquitoes with a genetic trait that confers resistance to malaria or causes population suppression; and, to drive the new trait through field populations. This review examines these two issues, and describes the groundwork that has been done towards understanding of the complex relation between the parasite and its vector.