This review summarizes our present understanding of Na-K-Cl cotransport and its physiological role in absorption and secretion of electrolytes and water in epithelial tissues. In the past several years an extensive literature about this cotransporter has developed due to its widespread distribution in a variety of cell types and its essential role in fluid and electrolyte transport in several epithelial tissues. We summarize this literature and speculate on the future characterization of this transport system. Although this review focuses on cotransport as it relates to absorptive and secretory processes in epithelia, important information concerning the pharmacology, stoichiometry, and regulation of Na-K-Cl cotransport in nonepithelial systems (i.e., erythrocytes, fibroblasts, squid axon, etc.) has been included to supplement areas that are less well established in the epithelial literature.