The development and implementation of the release of genetically modified mosquitoes (GMM) for interrupting pathogen transmission represent a major challenge, despite the fact that several achievements have been made about Anopheles and Aedes mosquitoes. There are major biotechnology challenges remaining about the improvement of the stability of a gene construct and its expression for a robust and complete interruption of pathogen transmission and the devise of safe means of spreading foreign antipathogen genes through mosquito populations in the wild. The implementation obstacles to overcome include proper risk assessment and management, conduct of studies to ensure safety for humans and the environment, devise of appropriate control strategies based on sound gene-driving systems, address properly ethical, legal and social implications of the release of GMM and public concerns. Although the development of GMM as disease-control tool is technically feasible, for proper implementation no field release must be undertaken until clear scientific proof of safety for humans and the environment and efficacy is provided and ELSI concerns and public acceptance are properly addressed.