Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The presence of lactoferrin in body fluids is proportional to the flux of neutrophils and its assessment can provide a reliable biomarker for inflammation. In gastrointestinal diseases increased fecal lactoferrin is a sensitive and specific surrogate marker for inflammatory bowel diseases in patients with chronic diarrhea and pain, and ascites lactoferrin can also provide a promising and reliable biomarker for bacterial peritonitis. Lactoferrin in pancreatic juice and stone could provide pathophysiological information of protein plug and stone formation in the pancreatic duct. Serum anti-lactoferrin autoantibody might contribute to the clarification of the pathogenetic mechanisms of autoimmune pancreatitis and liver diseases, although its diagnostic and prognostic value appears to be limited. Further studies will be necessary to elucidate the exact details.