The discovery that cholecystokinin (CCK) acts on CCK1 receptors on vagal afferent fibers to mediate pancreatic secretion, together with the observations that the most inhibitory mediators of pancreatic exocrine secretion target the dorsal vagal complex, led to a paradigm shift in the understanding of the control of pancreatic secretion, with recognition that pancreatic secretion is under neurohormonal control rather than direct hormonal control. Insulin plays a significant role in modulating exocrine pancreatic secretion. Mediation of postprandial pancreatic secretion has been ascribed mainly to the hormones secretin and CCK and to vagovagal reflexes that activate cholinergic postganglionic neurons in the pancreas. This chapter summarizes the role of intracellular messengers and effectors in pancreatic enzyme secretion. It addresses inhibitory phases and feedback regulation of pancreatic secretion. Administration of motilin antiserum abolishes the cyclic pattern of pancreatic secretion.