Every year, approximately 700,000 people die from complications associated with etiologic disease agents transmitted by mosquitoes. While insecticide-based vector control strategies are important for the management of mosquito-borne diseases, insecticide-resistance and other logistical hurdles may lower the efficacy of this approach, especially in developing countries. Repellent technologies represent another fundamental aspect of preventing mosquito-borne disease transmission. Among these technologies, spatial repellents are promising alternatives to the currently utilized contact repellents and may significantly aid in the prevention of mosquito-borne disease if properly incorporated into integrated pest management approaches. As their deployment would not rely on prohibitively expensive or impractical novel accessory technologies and resources, they have potential utility in developing countries where the burden of mosquito-borne disease is most prevalent. This review aims to describe the history of various repellent technologies, highlight the potential of repellent technologies in preventing the spread of mosquito-borne disease, and discuss currently known mechanisms that confer resistance to current contact and spatial repellents, which may lead to the failures of these repellents. In the subsequent section, current and future research projects aimed at exploring long-lasting non-pyrethroid spatial repellent molecules along with new paradigms and rationale for their development will be discussed.