Fusarium head blight (FHB), caused by Fusarium graminearum, has caused important yield and quality losses in wheat crops (Triticum aestivum) in subtropical southern Brazil in the last decade. The latest severe epidemics occurred in 2012, 2014, 2015 and 2018, with a frequency of four occurrences every ten years. Our past experience showed that the control of FHB in wheat and associated mycotoxins is unsatisfactory when a single control strategy is implemented. Due to this fact, the Cooperativa Agrária Agroindustrial, located in southern Paraná State, Brazil, developed the integrated management of FHB and associated mycotoxins [mainly deoxynivalenol (DON)], which presents two main phases: preharvest and post-harvest strategies. Among the pre-harvest strategies we have emphasized the genetic resistance strategy, which aims to reduce mycotoxin levels in wheat grains and in whole grain flour (WGF) by studying the reaction of wheat genotypes to FHB and the production of DON. Irrigated field trials inoculated with a pool of 10 isolates representing the genotypes of trichothecenes from the Fusarium graminearum species complex occurring in the region were conducted with different wheat genotypes for five years. There were differences between wheat genotypes regarding the incidence and severity of FHB and DON levels in years of weak to moderate epidemics. The use of the genetic resistance strategy proved viable in years occurring weak to moderate FHB epidemics allowing the reduction of the levels of DON in wheat grains and consequently in WGF. However, especially in years of severe epidemic of FHB, this strategy should be adopted in conjunction with the other pre and post-harvest strategies.