The unintentional arrival of the cactus moth, Cactoblastis cactorum (Berg), in Florida has raised concerns for the safety of native and rare Opuntia species in the Florida Keys and the potential spread of C. cactorum to the Opuntia-rich areas of the western United States and Mexico. In addition to threatening the biodiversity of these native ecosystems, such non-target effects would generate negative publicity that could heighten public concern over the use of exotic natural enemies and jeopardize future biological control programs against weeds. In this paper we discuss the use of inherited (F1) sterility in Lepidoptera to study, predict, and manage the expanding populations of C. cactorum. Research areas in which the use of F1 sterility would be most applicable include (1) elucidation of the host range of C. cactorum for key native Opuntia species from across the U.S., (2) prediction of the geographic range of C. cactorum in the U.S. and Mexico, and (3) delineation of the impact of native natural enemies on the spread of C. cactorum. The use of F1 sterility for control of C. cactorum would be most appropriate for (1) eradication of C. cactorum from areas of new introductions, or from isolated and/or environmentally sensitive areas such as the Florida Keys, (2) establishment of a barrier by means of release of irradiated moths along the leading edge of the C. cactorum geographical range, and (3) provisioning sterile C. cactorum in the field as hosts for released natural enemies to increase their initial survival and establishment.