Recent advances in technology have made strategies for disease control using genetically modified (GM) vectors more plausible. Selecting an appropriate field site for research with GM mosquitoes may be one of the most complex and significant aspects of the research process. Among the key considerations of the process is the need to address ethical, legal, and cultural (ESC) issues. No guidelines have been developed to date for this complicated and sensitive process. In this paper, we describe a site selection process and a set of preliminary considerations for addressing the ESC aspects of a research program involving genetic strategies for the control of mosquitoes as vectors for dengue viruses. These considerations reflect some of the key ESC issues for site selection decisions for research with GM vectors.