The epithelial sodium channel (ENaC) is a heteromeric channel composed of three similar but distinct subunits, α, β and γ. This channel is an end-effector in the rennin-angiotensin-aldosterone system and resides in the apical plasma membrane of the renal cortical collecting ducts, where reabsorption of Na(+) through ENaC is the final renal adjustment step for Na(+) balance. Because of its regulation and function, the ENaC plays a critical role in modulating the homeostasis of Na(+) and thus chronic blood pressure. The development of most forms of hypertension requires an increase in Na(+) and water retention. The role of ENaC in developing high blood pressure is exemplified in the gain-of-function mutations in ENaC that cause Liddle's syndrome, a severe but rare form of inheritable hypertension. The evidence obtained from studies using animal models and in human patients indicates that improper Na(+) retention by the kidney elevates blood pressure and induces salt-sensitive hypertension.