Diseases caused by pathogenic viruses, bacteria, oomycetes, and fungi are a major threat to cereal production worldwide. However, cereal plants have evolved a plethora of disease resistance genes to combat such threats. This genetic resistance forms an essential component of plant protection and is exploited by breeders to develop crop cultivars with high levels of field resistance. Despite the importance of disease resistance for crop improvement, only a minority of the disease resistance genes has been isolated from cereal genomes and molecularly studied so far. Here, we highlight the latest advancements in cereal genomics that have facilitated the rapid isolation of cereal resistance genes. A particular focus will be given to barley and wheat, two cereal species with particularly large and complex genomes. As a case study, we will discuss the recent cloning of the wheat Stb6 resistance gene, for which several new genomics approaches have been combined.