The human pancreatic ductal epithelium secretes 1–2L of alkaline fluid every day which may contain up to 140mM NaHCO₃. Until the last couple of years most of the scientists believed that the physiological function of this alkaline secretion is to wash digestive enzymes down the ductal tree and into the duodenum, and to neutralise acidic chyme entering the duodenum from the stomach. However, most recently we suggested that there are at least two other important physiological roles of bicarbonate inside the pancreas: i) to neutralise protons secreted by acinar cells and ii) to curtail trypsinogen autoactivation within the pancreatic ductal system. Therefore, derangements of bicarbonate secretion will decrease luminal pH which will promote the autoactivation of trypsinogen. Trypsin will further inhibit bicarbonate transport leading to a vicious cycle generating further falls in luminal pH and enhanced trypsinogen activation, which will favour the development of pancreatitis. There are of course other important lines of evidence supporting the idea that pancreatic ducts play part in the pathogenesis of pancreatitis: i) ductal fluid and bicarbonate secretion are compromised in acute and chronic pancreatitis, ii) one of the main endpoints of chronic pancreatitis is the destruction of the ductal system, iii) mutations in CFTR may increase the risk of pancreatitis, and iv) etiological factors for pancreatitis, such as bile acids or ethanol in high concentration, inhibit pancreatic ductal bicarbonate secretion. In summary, pancreatic ductal bicarbonate secretion is a very important field of research which needs much more attention.