Coeliac disease is a permanent intolerance to wheat gliadins and related prolamines. Patients who have an obvious malabsorption syndrome form only a small minority of the total number of people with coeliac disease. There are, in fact, no pathognomonic clinical features, and the condition is defined and diagnosed by the presence of pathological changes in the small bowel mucosa related to the presence of toxic prolamines. Susceptibility to coeliac disease is determined to a significant extent by genetic factors. A large part of the genetic susceptibility maps to the HLA region on chromosome 6, as approximately 95% of coeliac disease patients carry an almost identical HLA DQ2/heterodimer; a role of non-HLA genes has also been postulated. From a pathogenetic point of view, most evidence supports the notion of a DQ-restricted gluten-specific Th1 response in the lamina propria; nonetheless, it is possible that, in coeliac subjects, gluten, prior to T cell activation, could exert a direct toxic effect leading to the production of proinflammatory signals.