Adaptation by pest insects to the bacterium Bacillus thuringiensis (Bt) can alter their susceptibility to other pathogens. As the number of acres planted in crops engineered to produce Bt toxin increases, many key agricultural pests are under strong selection to evolve resistance to Bt. In conjunction with a refuge strategy, fitness costs of Bt resistance can slow or prevent resistance. Fitness costs occur when, in the absence of Bt toxin, resistant insects are less fit than susceptible insects. We discuss evidence indicating that Bt resistance carriers a fitness cost of increased susceptibility to other pathogens, focusing on interactions between the pink bollworm Pectinophora gossypiella and the entomopathogenic nematode Steinernema riobrave. Current evidence suggests that insect pathogens may be used synergistically with Bt crops to enhance resistance management and suppress pest populations.