The intestinal mucosal immune system is one of the largest immunological compartments in the body. This chapter summarizes basic concepts of general and mucosal immunology and how these are involved in various diseases of the gastrointestinal tract. Intestinal cryptopatches and isolated lymphoid follicles are two lymphoid structures within the mucosal immune system. Abnormalities in the mucosal immune system underlie a broad range of gastrointestinal diseases. The chapter provides a survey of the gastrointestinal, liver, and pancreatic diseases in which immunological abnormalities are known to contribute to disease pathogenesis. Inflammation is a prominent component of several important gastrointestinal diseases, including gastroesophageal reflux disease, Helicobacter pylori gastritis, eosinophilic gastritis, peptic ulcer disease, inflammatory bowel disease (IBD), celiac disease, pancreatitis, primary sclerosing cholangitis, autoimmune hepatitis, and various other enteric infections. The inflammatory response can be viewed as an effector mechanism for the immune response.