Mosquitoes transmit deadly diseases. Chemical repellents deter mosquitoes from approaching or biting a human host and are an effective behavior-based method of personal protection. However, the current standards for selecting repellents often disregard their mode of action. This has likely led many potential repellents to be overlooked. Here, we discuss the sensory systems that underlie host-seeking behavior and how such behaviors are interrupted by repellents. We explore the behavioral assays used to identify repellents and how these have led a handful of contact repellents (DEET, picaridin, IR3535) to dominate the field. Finally, we consider how the development of spatial repellents may further protect against mosquito-borne diseases.