Wheat grains have a complex structure which contains an organized distribution of nutrients. Cooking induces gluten formation. Celiac Disease and Wheat Allergy are well known wheat-related disorders, the first being a gluten-dependent autoimmune enteropathy, the latter a hypersensitivity IgE - mediated reaction. The pathogenetic mechanism of non-celiac gluten sensitivity is still under investigation. The clinical diagnosis is: the presence, in relation to the ingestion of gluten containing foods, of intestinal and extra- intestinal symptoms in patients where celiac disease and wheat allergy have already been excluded. There is ongoing evidence that non- gluten derived proteins have an important pathogenetic role in non-celiac gluten sensitivity and probably also in celiac disease: Amylase Trypsin Inhibitors-ATIs are proteins that are also present in rye and barley; they are triggers of innate immune response in non-celiac gluten sensitivity. They may also exacerbate immunomediate inflammatory bowel diseases. Gluten-free diet is the only effective therapy both in celiac disease and non-celiac gluten sensitivity. Alternative therapeutic strategies are under investigation in Celiac Disease: -exogenous enzyme gluten digestion to obtain less toxic fragments; - molecules able to be remodeling enterocyte tight junctions which become permeable in celiac disease. Researches should be devoted to creating a less toxic grain, while to date grain has been genetically modified to increase gluten content. We advise a future for researches in agronomy. A role for functional and nutraceutical foods must be investigated. Another emerging issue is due to the consciousness of wheat/gluten-microbiota-brain and mind interactions.