AbstractBackground and ObjectivesResearch on wheat grain proteins is reviewed, including achievements over the past century and priorities for future research. The focus is on three groups of proteins that have major impacts on wheat quality and utilization: the gluten proteins which determine dough viscoelasticity but also trigger celiac disease in susceptible individuals, the puroindolines which are major determinants of grain texture and the amylase/trypsin inhibitors which are food and respiratory allergens and are implicated in triggering celiac disease and nonceliac wheat sensitivity.FindingsAlthough earlier work focused on protein structure and properties, the development of genomics and high‐sensitivity proteomics has resulted in the availability of a vast amount of information on the amino acid sequences of individual wheat proteins, including allelic variants of gluten proteins which are associated with good processing quality and of puroindolines, which are associated with a hard or soft grain texture, and on protein expression and polymorphism.ConclusionsHowever, our ability to exploit this knowledge is limited by a lack of detailed understanding of the structure:function relationships of wheat proteins. In particular, we need to understand how the three‐dimensional structures of the individual proteins determine their interactions with other grain components (to determine functional properties) and with the immune systems of susceptible consumers (to trigger adverse responses), how these interactions are affected by allelic variation, and how they can be manipulated.Significance and NoveltyThe article, therefore, identifies priorities for future research which should enable the adoption of a more rational approach to improving the quality of wheat grain proteins.