Celiac disease (CD) is a syndrome characterized by damage of the small intestinal mucosa caused by the gliadin fraction of wheat gluten and similar alcohol-soluble proteins (prolamines) of barley and rye in genetically susceptible subjects. The presence of gluten in these subjects leads to self-perpetuating mucosal damage, whereas elimination of gluten results in full mucosal recovery. The clinical manifestations of CD are protean in nature and vary markedly with the age of the patient, the duration and extent of disease, and the presence of extraintestinal pathologic conditions. In addition to the classical gastrointestinal form, a variety of other clinical manifestations of the disease have been described, including atypical and asymptomatic forms. Therefore, diagnosis of CD is extremely challenging and relies on a sensitive and specific algorithm that allows the identification of different manifestations of the disease. Serologic tests developed in the last decade provide a noninvasive tool to screen both individuals at risk for the disease and the general population. However, the current gold standard for the diagnosis of CD remains histologic confirmation of the intestinal damage in serologically positive individuals. The keystone treatment of CD patients is a lifelong elimination diet in which food products containing gluten are avoided.