In the kidney, thiazide and loop diuretics are secreted from proximal tubule via organic anion transporters and bind to apical sodium transporters, viz. the Na⁺-Cl^– cotransporter in the distal convoluted tubule and the Na⁺-K⁺-2Cl^– cotransporter in the thick ascending limb, respectively. Studies in animal models suggest that expression of the transporters may be affected by long-term diuretic administration at the target sites of renal tubule as well as at downstream segments. This information will be of help in understanding the adaptive responses to long-term diuretic use.