Non-celiac gluten sensitivity (NCGS) has been introduced recently as a potentially common disease on the basis of studies of patients with claimed reactivity to gluten but without the characteristics of celiac disease (CD). CD is characterized by antibody reactivity toward the autoantigen transglutaminase 2, characteristic histological abnormalities of the small intestine, and an almost obligatory genetic haplotype (HLA-DQ2 or DQ8). The diagnosis of NCGS is based largely on the clinical suspicion of hyper-reactivity to gluten and the absence of the characteristics of CD. Few published studies have used double-blind placebo-controlled food challenges (DBPCFCs) for the diagnosis of NCGS, and none in children. Innate immune reactivity to amylase trypsin inhibitors has been suggested as the pathogenic principle in NCGS, but confirmatory evidence is lacking. Also, further clinical studies including DBPCFCs are needed.