The consumption of wheat-based products is high in most Western countries (e.g. Europe, United States) and is increasing in Eastern countries as a consequence of a shift toward a Western lifestyle. Historically, Wheat-Related Disorders (WRD) referred only to wheat allergy and celiac disease. In recent years, a growing number of subjects worldwide have reported intestinal and extraintestinal symptoms, without the diagnostic features of celiac disease or wheat allergy. In these subjects, symptoms of a wheat-related disorder may originate from non-celiac gluten sensitivity, the non-gluten antibody target protein serpins, purinins, α-amylase/protease inhibitors, globulins, farinins, wheat exorphin sensitivity, wheat germ agglutinin sensitivity, wheat amylase-trypsin inhibitor sensitivity, and/or FODMAP (fermentable oligo-, di-, mono- saccharides and polyols) sensitivity. This article reviews the pertinent literature and presents three pediatric cases of wheat-related disorders that present with varied clinical presentations: liver failure, type 1 diabetes mellitus and a conjunctival tumor believed to be Kaposi’s sarcoma. All conditions responded rapidly to a wheat-free diet. A wheat-related disorder (with or without celiac disease) may affect any organ or system including cardiovascular disease, neurological diseases, connective tissue diseases, allergies, infammatory bowel disease, nephritis and others. While there is increasing awareness that wheat-related disorders can manifest with extra-intestinal symptoms, clinicians still rely too heavily on the presence of gastrointestinal symptoms to suspect a wheat-related disorder. These three cases showed wheat-related pathogenesis affecting diverse organs, such as the liver, pancreas, or eye, without marked gastrointestinal symptoms. Therefore, in patients with unexplained symptoms, who do not improve with standard therapies, it may be prudent to screen for serological indicators of a WRD. Clinical awareness of the diversity of presentations of a WRD may lead to earlier suspicion, investigation and a reduction in co-morbiditie.