Technical Abstract: The use of mixtures of insecticidal seed and non-toxic seed to provide an in-field refuge for susceptible insects in an insect-resistance-management (IRM) plan has been considered for at least two decades, but the US Environmental Protection Agency has only recently authorized their use in commercial production. The purpose of this commentary is to explore issues that regulators, industry and other stakeholders should consider as we expand the use of biotechnology and consider the use of seed mixtures as a major tactic in IRM. We discuss how block refuges and seed mixtures in transgenic insecticidal corn production will impact integrated pest management (IPM) and the evolution of pest resistance. We conclude that seed mixtures will make pest monitoring more difficult. We also conclude that seed mixtures may make IRM riskier because of larval behavior and greater adoption of insecticidal corn. On the other hand, block refuges are riskier because of adult pest behavior and the lower compliance with IRM rules expected from farmers. It is likely that secondary pests not targeted by the insecticidal corn as well as natural enemies will be handled differently in block refuges and seed mixtures.