Pancreatic ductal epithelial cells play a fundamental role in HCO3 (-) secretion, a process which is essential for maintaining the integrity of the pancreas. Although several studies have implicated impaired HCO3 (-) and fluid secretion as a triggering factor in the development of pancreatitis, the mechanism and regulation of HCO3 (-) secretion is still not completely understood. To date, most studies on the ion transporters that orchestrate ductal HCO3 (-) secretion have focussed on the role of Cl(-)/HCO3 (-) exchangers and Cl(-) channels, whereas much less is known about the role of K(+) channels. However, there is growing evidence that many types of K(+) channels are present in ductal cells where they have an essential role in establishing and maintaining the electrochemical driving force for anion secretion. For this reason, strategies that increase K(+) channel function may help to restore impaired HCO3 (-) and fluid secretion, such as in pancreatitis, and therefore provide novel directions for future pancreatic therapy. In this review, our aims are to summarize the types of K(+) channels found in pancreatic ductal cells and to discuss their individual roles in ductal HCO3 (-) secretion. We will also describe how K(+) channels are involved in pathophysiological conditions and discuss how they could act as new molecular targets for the development of therapeutic approaches to treat pancreatic diseases.