Celiac disease (CD) is an autoimmune disorder, which damages the small intestine and is caused by ingestion of gluten in genetically susceptible individuals. The only known effective treatment is a lifelong gluten-free diet. Genetic risk factors have been identified and nearly all patients are HLA-DQ2 and/or HLA-DQ8 positive. Specific autoantibodies, IgA antitissue transglutaminase-2, antiendomysium, and antideaminated forms of gliadin peptide antibodies, are widely used as diagnostic aids in celiac patients. However, the discovery of new biomarkers may help in the diagnosis and follow-up of the disease. Recently, the molecule REG Iα, involved in tissue regeneration, has been proposed as a new biomarker of CD. REG Iα expression is increased in the target tissue and in the sera of celiac patients during damage and inflammation, decreasing after gluten-free diet. In this article we review the main biomarkers for diagnosis and monitoring of CD, focusing on the immune response-related mechanisms.