Topical chemical insect repellents are used in an attempt to protect ourselves from biting insects and the pathogens that they transmit. Unfortunately, the search for newer and better repellents has not been highly successful. One important reason is that we do not know how insect repellents work. Various theories that have been proposed are reviewed here. In addition, information obtained from sensory physiological studies is presented, which suggests that there may be more than 1 sensory-behavioral mechanism by which chemical insect repellents reduce the biting activity of female mosquitoes. Repellents may act by interfering with the perception of host-attractant signals, by exciting a receptor for a competing behavior, by switching a sensory message from attraction to repulsion, by activating several different receptor systems so that the repellent, in effect, “jams” meaningful sensory information, and/or by exciting a repellent (i.e., noxious substance) receptor.