Non-celiac gluten sensitivity (NCGS), sometimes known as non-celiac wheat sensitivity (NCWS), has recently received much attention, both scientific as well as from the alternative medical community. Over the past 5 years, there are over 200 publications on NCGS indexed on the PubMed database, the gluten-free market has been growing bigger, and it is clear that the number of consumers who are on a gluten-free diet (GFD) possibly because of a suspicion for NCGS appears to grow even faster. Nevertheless, despite these three rising events, many questions about NCGS remain unresolved. It is likely that NCGS represents a heterogeneous group of disorders linked by a common response to a GFD. It is still not fully understood how gluten, and likely other wheat proteins and components, could activate and drive the pathophysiology of NCGS. As a result, there are still no clear biomarkers, no robust clinical diagnostic criteria, nor a conclusive definition for NCGS. This heterogeneity can be approached by reducing the variables, in particular those of human behaviour and placebo effect, by studying animal models to address specific biological effects of wheat andlor gluten-related proteins. fIcrein we review the animal models and their potential to be used to advance our understanding of these disorders and potentially address their prevention and treatment.