Mosquitoes are serious vectors of diseases threading millions of humans and animals worldwide, as malaria, filariasis, and important arboviruses like dengue, yellow fever, chikungunya, West Nile virus, and Zika viruses. The swift spread of arboviruses, parasites, and bacteria in conjunction with the development of resistance in the pathogens, parasites, and vectors represents a great challenge in modern parasitology and tropical medicine. Unfortunately, synthetic insecticides had led to some serious health and risk concerns. There are no vaccines or other specific treatments for arboviruses transmitted by mosquitoes. Accordingly, avoidance of mosquito bites remains the first line of defense. Insect repellents usually work by providing a vapor barrier deterring mosquitoes from coming into contact with the skin surface, and this chapter focused on assets and liabilities, mechanism of action, improving efficacy, safety, and future perspective of synthetic and natural repellents that could potentially prevent mosquito-host interactions, thereby playing an important role in reducing mosquito-borne diseases when used correctly and consistently.