Celiac Disease is a worldwide spread condition affecting 1:100-1:200 individuals. It is a permanent food intolerance to ingested gluten in genetically predisposed subjects. In this review we analyze the biochemical markers of the disease going from laboratory findings to histology passing through genetics. Gluten intolerance is a unique model of autoimmune disease in which we can recognize the main environmental factor (gluten) and the more complex genetic background. In additional way, serological markers for monitoring the disease and a safe and effective therapy (gluten free diet) are also available. In deed the environmental factor such as gluten intake is necessary to trigger the disease but genetics also matter. HLA genes are the most studied but in recent times also not HLA related genes are giving proof of additional relative risk to disease if present. From histological point of view intra epithelial cell infiltration by several lymphocyte subsets is becoming more and more important also for understanding pathogenesis of the disease.