Wheat is one of the world’s major crops and is at the basis of human nutrition in several countries. The main protein components of the wheat seed are gliadins and glutenins, which belong to the prolamin protein family and accumulate in endosperm cells during seed development. Although these proteins have been widely studied for decades, some aspects of their genomic organisation have been revealed only recently by genomic studies that used both classical and next-generation experimental approaches. Since prolamins influence technological characteristics of wheat flours which are important for the production of a wide range of foods, this information is functional to the development of breeding strategies focused on grain quality. The aim of this chapter is to discuss studies on the structural organization of wheat prolamin loci, on the transcriptional differences between different family members and on their evolution. Available information relating to the durum wheat genome is discussed in the general framework provided by studies on diploid, tetraploid and hexaploid wheats and on donor species.