Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration in the epithelial membrane and the lamina propria, and expression of multiple cytokines and other signaling proteins. The disease leads to inflammation, villous atrophy, and crypt hyperplasia in the small intestine. In addition to the intestinal symptoms, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits. Gluten-free diet is currently the only effective mode of treatment for celiac disease, but better understanding of the mechanism of the disease is likely to add other choices for therapy in the future.