Coeliac disease (CD) is a permanent intolerance to gluten that provokes alterations in the mucosa of the small intestine. The disease can usually be controlled by excluding gluten from the diet. CD is immunologically-mediated, with a strong linkage to certain HLA alleles and a permanently altered intraepithelial lymphocytes (IEL) pattern. The development of a flow cytometric technique for the evaluation of IEL subsets has increased our understanding of these alterations and has prepared the ground for its clinical application. Our experience shows that this procedure has excellent sensitivity and specificity in the diagnosis of CD and that it is particularly useful in the evaluation of atypical presentations of the disease. The present article reviews our experience in the diagnosis of CD and discusses some of the hypotheses that have been put forward on the possible role of IEL in its pathogenesis.