The recent discovery of efflux transporters in the gut has revolutionized our understanding of the absorption and bioavailability of pharmaceuticals and other xenobiotics in humans. Despite the celebrity of efflux transporters in the areas of pharmacology and medicine, their significance is only beginning to be realized in the area of plant-herbivore interactions. This review integrates reports on the importance of gut efflux transporters to diet selection by herbivores. The diets of herbivores are laden with toxic plant secondary metabolites (PSMs) that until recently were thought to be processed almost exclusively by detoxification enzymes in the liver. We describe how efflux transporters in the gut may play a critical role in regulating the absorption of PSMs in herbivores and dictating diet selection. Recent studies suggest that the role of efflux transporters in mediating diet selection in herbivores may be as critical as detoxification enzymes. In addition to diet selection, gut efflux transporters have implications for other aspects of plant-animal interactions. They may be significant components of the evolutionary arms race that influences chemical diversity in plants. Furthermore, in agricultural systems, gut efflux transporters may play an important role in the effectiveness of pesticides. This synthesis paper introduces a new direction in plant-herbivore interactions by providing a complementary mechanism, regulated absorption, to detoxification that may define tolerance to PSMs by herbivores.