The recently adopted conservation and minimum tillage practices in wheat-production systems coupled with the concomitant warming of the Earth are believed to have caused the upsurges in Fusarium head blight (FHB) prevalence in major wheat-producing regions of the world. Measures to counter this effect include breeding for resistance to both initial infection of wheat and spread of the disease. Cases of mycotoxicosis caused by ingestion of wheat by-products contaminated with FHB mycotoxins have necessitated the need for resistant wheat cultivars that can limit mycotoxin production by the dominant causal pathogen, Fusarium graminearum. This manuscript reviews breeding tools for assessing and improving resistance as well as limiting mycotoxin contamination in wheat to reflect on the current state of affairs. Combining these aspects in wheat research and development promotes sustainable quality grain production and safeguards human and livestock health from mycotoxicosis.