Fungicide resistance is a key issue that affects crop yield and food security, and scientists have therefore debated for decades, with equivocal conclusions, whether the practice of alternation or using mixtures of active ingredients is best for managing fungicide resistance. Using a new mathematical model that properly normalizes for the level of disease control, Elderfield et al. demonstrate that the best strategy is almost always to spray fungicides in a mixture. They further show how simple epidemiological reasoning can explain this very general and practically important result.