Na+,K(+)-ATPase plays a major role in the reabsorption of sodium by the kidney. This organ is highly heterogeneous, and its functional unit, the nephron, is formed of successive epithelia with specific morphological and functional characteristics. Na+,K(+)-ATPase expression varies along the nephron. Variations in the catalytic activity of the pump, the number of active pumps expressed in the basolateral membrane, its substrate dependency towards Na and K, and its sensitivity to the inhibitor ouabain have been observed in distinct tubular segments. Most authors agree on the large (or unique) prevalence of the alpha 1 and beta 1 isoforms of the two subunits of Na+,K(+)-ATPase in each nephron segment, although at different levels. The cortical collecting duct represents a unique epithelium to study the physiological relevance of the regulation of Na+,K(+)-ATPase activity, including an immediate substrate activation, a rapid recruitment of active pumps from a reserve pool, and long-term hormonal effects. Whether these functions require other molecular determinants than the alpha 1 and beta 1 isoform subunits remains to be established.