Insecticides that kill the mosquito and drugs that kill the parasite are the only weapons presently available to fight the unbearably high human malaria toll. As mosquito and parasite resistance to these agents limits their effectiveness and there is currently no effective malaria vaccine available, clearly new means to fight the disease must be developed. This chapter explores the feasibility of an alternative strategy: rather than kill the vector mosquito, modify it to render it incapable of sustaining parasite development. This chapter investigates genetically modifying the symbiotic bacteria that naturally occur in the mosquito’s midgut, by producing bacteria that carry the same anti-parasite genes. Major remaining challenges are to devise means to introduce the modified bacteria into mosquitoes in the field and to resolve regulatory and ethical issues related to the release of genetically modified organisms in nature.