Coeliac disease is a lifelong intolerance to gluten affectinggenetically predisposed individuals. HLA genes are the main genetic factors,and the risk variants coding for the proteins HLA-DQ2 and HLA-DQ8 are necessaryfor the development of the disease. Although these variants are present in 30%of the general population, the prevalence of the disease is around 1%. Thus,other genetic as well as environmental factors are involved. Gluten is thestorage protein found in wheat, barley, rye and oats. Undigested glutenpeptides are the triggers of an abnormal immune response in the smallintestine, characterized by a chronic inflammation and autoimmunity. Villousatrophy in the duodenum, or even milder intestinal lesions, are key features ofthe disease, but other associated conditions can also occur. Gluten consumptionhas extended worldwide since mankind started wheat cultivation around 10,000years ago. The prevalence of coeliac disease has also increased over time,especially during the 20^th century, in parallel with the glutenenrichment of wheat as a result of crossbreeding programs and the use of glutenin the food industry. The evolutionary role of HLA risk variants is yet to besolved.