The understanding of the pathogenesis of celiac disease has made huge advances in recent years. The disease is caused by an inappropriate immune response to dietary gluten proteins. This immune response is controlled by CD4(+) T cells in the lamina propria that recognize gluten peptides in the context of disease predisposing HLA-DQ2 and HLA-DQ8 molecules.(1, 2) These T cells are specific for proline- and glutamine-rich gluten peptides that are resistant to proteolysis and that have been become deamidated by the enzyme transglutaminase 2 (TG2). Strikingly, celiac disease patients produce antibodies to this same enzyme when exposed to dietary gluten. Here we discuss how the new insight in the pathogenesis has lead to development of new diagnostics and nourished research into novel treatments.