Symbioses between eukaryotes and unicellular organisms are quite common, with examples copiously disseminated throughout the earth's biota. Arthropods, in particular, owe much of their ecological success to their microbial flora, which often provide supplements either lacking in the limited host diet or which the hosts are unable to synthesize. In addition to harboring beneficial microbes, many arthropods (vectors) also transmit pathogens to the animals and plants upon which they prey. Vector-borne diseases exact a high public health burden and additionally have a devastating impact on livestock and agriculture. Recent scientific discoveries have resulted in the development of powerful technologies for studying the vector's biology, to discover the weak links in disease transmission. One of the more challenging applications of these developments is transgenesis, which allows for insertion of foreign DNA into the insect's genome to modify its phenotype. In this review, we discuss an approach in which the naturally occurring commensal flora of insects are manipulated to express products that render their host environment inhospitable for pathogen transmission. Replacing susceptible insect genotypes with modified counterparts with reduced pathogen transmission ability, might provide a new set of armaments in the battle for vector-borne disease reduction.