A Bt soybean has been recently developed, thus, efficiently regulating the populations of major lepidopteran pests. However, in other cases, these benefits have been reduced or lost because of the rapid evolution of pest resistance to the Bt toxins in transgenic crops. When pest populations are exposed to Bt crops and to refuges (non-Bt plants), the evolution of resistance is governed by the fitness of resistant individuals relative to susceptible individuals for both the presence and absence of Bt toxins. One major ecological concern regarding the biosafety of Bt crops on the environment is their potential effects on non-target organisms, especially predators and parasitoids that play an important role in pest control. This information is important for supporting insect resistance management (IRM) programs and for improving agricultural practices in a crop production system with Bt plants. Before the use of Bt plants for insect pest control in Brazil is adopted, IRM programs should be established to ensure the sustainability of this technology for integrated pest management (IPM). This review presents data on Bt soybean and lepidopteran pests as well as on the importance of natural enemies as a form of biological control, and applications for IPM and IRM.