The serum/glucocorticoid-induced kinase Sgk1 plays an important role in the regulation of epithelial ion transport. This kinase is very rapidly regulated at the transcriptional level as well as via posttranslational modifications involving phosphorylation by the MAP or PI-3 kinase pathways and/or ubiquitylation. Although Sgk1 is a cell survival kinase, its primary role likely concerns the regulation of epithelial ion transport, as suggested by the phenotype of Sgk1-null mice, which display a defect in Na( homeostasis owing to disturbed renal tubular Na+ handling. In this review we first discuss the molecular, cellular, and regulatory aspects of Sgk1 and its paralogs. We then discuss its roles in the physiology and pathophysiology of epithelial ion transport.