Marker-assisted selection (MAS) provides opportunities for enhancing the response from selection because molecular markers can be applied at the seedling stage, with high precision and reductions in cost. About each of 50 genes conferring monogenic resistances and hundreds of quantitative trait loci (QTL) for quantitative disease resistances have been reported in wheat and barley. For detecting single-major gene resistance, MAS could be easily applied, but is often not necessary because the resistances are selected phenotypically. In quantitative disease resistances, MAS would be very useful, but the individual QTL often have small effects. Additionally, only a few monogenic resistances are durable and only a few QTL with high effects have been successfully transferred into elite breeding material. Further economic and biological constraints, e.g., a low return of investment in small-grain cereal breeding, lack of diagnostic markers, and the prevalence of QTL-background effects, hinder the broad implementation of MAS. Examples in which MAS has been successfully applied to practical breeding are the wheat rust resistance genes Lr34 and Yr36, the eyespot resistance gene Pch1, the recessive resistance genes rym4/rym5 to barley yellow mosaic viruses, mlo to barley powdery mildew, and two QTL for resistance to Fusarium head blight in wheat (Fhb1 and Qfhs.ifa-5A). Newly identified broad-spectrum resistance genes/QTL conferring resistance to multiple taxa of pathogens offer additional perspectives for MAS. In the future, chip-based, high-throughput genotyping platforms and the introduction of genomic selection will reduce the current problems of integrating MAS in practical breeding programs and open new avenues for a molecular-based resistance breeding.