Gluten sensitivity has been best recognized and understood in the context of two conditions, celiac disease and wheat allergy. However, some individuals complain of symptoms in response to ingestion of “gluten,” without histologic or serologic evidence of celiac disease or wheat allergy. The term non-celiac gluten sensitivity (NCGS) has been suggested for this condition, although a role for gluten proteins as the sole trigger of the associated symptoms remains to be established. This article reviews the available information regarding symptomatology, epidemiology and genetics, serology and histology, and in vitro and in vivo experimental data on the pathophysiology of NCGS.