In the proximal tubule, sodium-dependent transport of phosphate (Pi) through the brush-border membrane represents the initial step in Pi reabsorption. cDNAs encoding several renal proximal tubule apical Na/Pi cotransport systems have been identified. These Na/Pi cotransporters are subdivided into type I (NaPi-1) and a type II (NaPi-2). Electrophysiological studies reveal that Pi transport by Na/Pi cotransporters is electrogenic. Regulation of proximal Pi reabsorption by dietary Pi intake and parathyroid hormone is primarily due to an alteration of apical type II Na/Pi cotransport; a rapid change of brush-border Na/Pi cotransport most likely occurs via an endo/exocytic mechanism. No evidence for physiological control of type I cotransporters has been obtained. Altered Pi reabsorption as observed in X-linked hypophosphatemia is largely via the type II Na/Pi cotransporter.