The strategies used in breeding disease-resistant wheat are informed by the importance and frequency of the disease, availability of resistant germplasm, genetics of resistance and means of selecting for resistance. Gene mapping to identify regions of the genome controlling important traits has been an important tool for plant geneticists and breeders. This chapter includes a case study of breeding for FHB resistance, illustrating the challenges and opportunities with an episodic disease, introgression of resistance genes from non-adapted germplasm and utilization of DNA marker technology. The use of quantitative trait locus mapping and breeding programme to develop rust-resistant germplasm are also described.