The epithelium of the excretory duct system of the exocrine pancreas secretes bicarbonate ions and mucins. Epithelial cells of the duct system also constitute primary sites of dysfunction in cystic fibrosis, pancreatitis and pancreatic cancer. The present work provides an overview of the current state of understanding of the physiology and pathophysiology of the pancreatic duct system and suggests approaches that will provide continued progress in exploration of the basic physiological processes operating in this tissue.