Celiac Disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins found in wheat, barley and rye. Contrary to common beliefs, this disorder is a systemic Disease with different manifestations, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly DQ2 and DQ8 classes. Previously, CD was considered to be a rare childhood disorder, but it is actually considered a frequent condition and can present at any age. Tissue transglutaminase (tTG) appears to be an important component of this Disease, both in its pathogenesis and its diagnosis and follow up. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive anti-endomysial antibody or tTG autoantibodies. The duodenal biopsy is considered to be the “gold standard” for diagnosis. Occasionally, it results in false-negative results because of patchy mucosal changes and that, in some patients, mucosal villous atrophy is more severe in the proximal jejunum which cannot be reached by routine endoscopes. Sometimes, the presentation of CD is with iron deficiency anemia, osteoporosis, dermatitis herpetiformis, persistent chronic hypertransaminasemia of unknown origin and neurologic disorder. The association of CD and endocrine Diseases, autoimmune disorders and various types of cancer is known. Treatment of CD is a strict, life-long gluten-free diet. Gluten-free diet results in remission of most symptoms.