Tight control of sodium reabsorption in the distal renal tubule is essential for extracellular volume homeostasis and long-term blood pressure control. Sodium entry from the tubule lumen into the cell occurs through apical epithelial sodium channels (ENaCs), which constitute the rate-limiting step of transepithelial sodium transport. The regulation of ENaC activity is therefore crucial to control this process. The most important stimulus for ENaC activity is the hormone aldosterone, although a multitude of other signals regulate channel function. The molecular mechanisms and signaling cascades involved in ENaC regulation have been the subject of intense research over the last few years. A major breakthrough in the field was the identification of the serum and glucocorticoid-induced kinase 1 (SGK1) as a potent activator of ENaC. SGK1 is a serine/threonine kinase structurally related to the family of AGC kinases. SGK1 is distinct among other AGC kinases by being regulated at multiple levels, including the biosynthesis and degradation of the protein, its activation by phosphatidylinositol-3-phosphate dependent kinase 1 (PDK1) and PDK2 and its subcellular localization. During my talk I will discuss recent advances in our understanding of ENaC regulation by SGK1 and the role that this kinase plays in hormonal control of transepithelial sodium transport. Work in my laboratory is funded by Ministerio de Educación y Ciencia (BFU2004-04433), Spain.