Among gluten-related disorders, gluten sensitivity is an emerging entity that is characterized by a wide array of manifestations. In particular, patients complain of IBS-like symptoms and extraintestinal manifestations that occur shortly after the ingestion of gluten. Symptoms improve or disappear when gluten is withdrawn from the diet, and recur if gluten is reintroduced. Laboratory tests are usually unhelpful for diagnosis, although ~50% of patients are positive for IgG antigliadin antibodies. The natural history of gluten sensitivity is unknown; in particular, it is still to be clarified whether this disorder is permanent or transient and whether it is linked to autoimmunity. The pathogenesis of gluten sensitivity is unclear; data so far demonstrate a predominant activation of innate immune responses. Further research is necessary to establish the main clinicopathological features of gluten sensitivity, thus enabling physicians to improve their management of the increasing number of patients who are sensitive to dietary gluten.