Epithelial Na channels (ENaCs) reside in the apical membrane of principal cells in the aldosterone-sensitive distal nephron, where they transport Na and have key roles in extracellular volume homoeostasis and blood pressure control. Specific proteases activate ENaC, a trimer composed of three structurally related subunits, by liberating inhibitory tracks imbedded in the extracellular regions of the alpha and gamma subunits. Extracellular Na inhibits ENaC by binding to sites within the extracellular regions of ENaC subunits, leading to a reduction in channel open probability. Recent findings regarding sites within ENaC subunits where inhibitory peptides and Na bind, and how these binding events affect channel gating will be reviewed.