major function of the intestinal epithelium is to control the amount of fluid entering into and being absorbed from the lumen[1]. In healthy conditions, net fluid movement follows an absorptive vector, although significant secretion also takes place to subserve digestive function. Thus, the secretion of fluid, driven by the active secretion of electrolytes, is important for maintaining the fluidity of intestinal contents during various stages of digestion and thereby allowing for diffusion of enzymes and nutrients. In the setting of disease, dysregulation of intestinal transport mechanisms may alter the balance between absorptive and secretory processes such that secretion predominates, leading to the clinical consequence of diarrhea. However, under conditions of both health and disease, fluid secretion is driven largely by the active secretion of chloride ions. Thus, there are both basic and clinical reasons for wishing to gain a full understanding of the basis and regulation of this transport process. The goal of my article, therefore, will be to review our understanding of intestinal chloride secretion and the ways in which it is regulated. Recent insights in this area enhancing our ability to intervene in diseases where chloride secretion is over-expressed, such as infectious and inflammatory diarrheal illnesses will also be discussed. This article will also cover the implications of intestinal secretory mechanisms for a genetic disease where chloride secretion is under-expressed, namely cystic fibrosis, where significant intestinal dysfunction, including obstruction and malabsorption,may also ensue.