Vector-borne diseases take an enormous toll on mankind, disproportionately affecting the poor and dispossessed in resource-poor settings. This symposium will examine the pathogen-mosquito vector relationships of two pandemic vector-borne diseases, malaria and dengue. Malaria, caused by protozoan parasites of the genus Plasmodium, and dengue, caused by flaviviruses, are transmitted by mosquitoes. While malaria is primarily a rural disease and dengue is an urban disease, the molecular approaches to pathogen-vector interactions of both diseases have important common themes. Delineating the molecular mechanisms by which these pathogens interact with their mosquito vectors is fundamental to developing novel strategies to interrupt disease transmission. Speakers in this symposium will describe their discoveries of molecular targets for blocking pathogen-vector interactions, mechanisms by which pathogens induce immune responses in the mosquito, mechanisms of malaria pathogenesis and vaccine development using human challenge models, development of transgenic mosquitoes to reduce the burden of malaria and dengue, and associated ethical and real-world field challenges to deploying transgenic insects to combat disease. The threat of parasites and pathogens to global health is increasing with globalization of our planet, and vector-borne disease management will be a key element in protection of humans against distribution of infectious agents by natural processes or bioterrorism.