Epithelial Na(+) channels (ENaC) form a highly regulated pathway for the reabsorption of Na(+) from urine. This regulation can take place at a number of different levels, including synthesis of channel protein, trafficking of the protein between the surface and internal membranes, proteolytic cleavage and channel gating. This article reviews the role of these different modes of regulation under physiological conditions and considers the possible contributions of dysregulation of these processes in disease states, particularly hypertension.