Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,“non-celiac gluten sensitivity”(NCGS)has been suggested to affect up to 6%of the United States public.While reliable clinical tests for CD exist,diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten.NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins.At present,an enormous food industry has developed to supply gluten-free products(GFP)with GFP sales in 2014 approaching$1 billion,with estimations projecting sales to reach$2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice.Features of NCGS and other gluten related disorders(e.g.,irritable bowel syndrome)call for a review of current distinctive diagnostic criteria that distinguish each,and identification of biomarkers selective or specific for NCGS.The aim of this paper is to review our current understanding of NCGS,highlighting the remaining challenges and questions which may improve its diagnosis and treatment. Currently, 1% of the United States population holds a diagnosis for celiac disease (CD), however, a more recently recognized and possibly related condition, “non-celiac gluten sensitivity” (NCGS) has been suggested to affect up to 6 % of the United States public.While reliable clinical tests for CD exist, diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal signals may provoked by gluten. NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins. At present, an enormous food industry has developed to supply gluten-free products (GFP) with GFP sales in 2014 approaching $ 1 billion, with estimations projecting sales to reach $ 2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice .Features of NCGS and other gluten related disor ders (eg, irritable bowel syndrome) call for a review of current distinctive diagnostic criteria that distinguish each, and identification of biomarkers selective or specific for NCGS. highlighting the remaining challenges and questions which may improve its diagnosis and treatment.