Mosquito repellents are used worldwide to prevent mosquito bites and mosquito-borne diseases. In order to develop more efficient and safer mosquito repellents, we first need to understand how currently used repellents work, or how they affect the mosquito’s sense of smell. At the Potter lab, we developed a method (calcium imaging) to visualize how sensory neurons on the antennae of the malaria mosquito respond to repellents. We found that natural repellents, such as lemongrass oil and eugenol, are able to activate some of these neurons. To our surprise, man-made repellents such as DEET did not activate any of these antennal neurons. This suggests that the malaria mosquito can smell natural repellents but not man-made repellents. We found that man-made repellents work in another way: They make neurons on the mosquito antennae respond less (or not at all) to the odors on our skin by decreasing the volatility of these odors. This means that instead of directly repelling the malaria mosquitoes away, man-made repellents prevent chemicals on our skin from evaporating and reaching the mosquitoes, rendering us invisible to them. We further showed that other species of mosquitoes, such as the yellow fever mosquito and the southern house mosquito, are directly repelled by DEET. This suggests that confusion in the field about how DEET works could be due to its species-specific effect. Our findings can help inform mosquito repellent choice by species, and streamline the discovery of improved insect repellents.