Human blood‐pressure is dependent on balancing dietary salt intake with its excretion by the kidney. Mendelian‐syndromes of altered blood pressure demonstrate the importance of the distal nephron in this process and of the thiazide‐sensitive pathway in particular. Gordon‐Syndrome(GS), the phenotypic inverse of the salt‐wasting Gitelman syndrome, is a condition of hyperkalaemic hypertension that is reversed by low dose thiazide diuretics or a low salt diet. Variants within at least four genes (the With‐No‐lysine‐(K)‐kinases, WNKs1&4, Cullin3 and KeLch‐like3) can cause the phenotype of GS. Details are still emerging for some of these genes, but it is likely that they all cause a gain‐of‐function in the thiazide sensitive Na‐Cl Cotransporter (NCC) and hence salt retention. We discuss the key role of a kinase, STE20(sterile 20)/SPS1‐related proline/Alanine‐rich Kinase(SPAK), that functions as an intermediary between the WNK kinases and NCC and whose loss‐of‐function mutation produces a Gitelman‐type phenotype in a mouse model. In addition to Mendelian blood pressure syndromes, the study of patients who develop Thiazide‐Induced‐Hyponatraemia(TIH) may give‐further molecular insights into the role of the thiazide‐sensitive pathway for salt reabsorption. We discuss the key features of TIH including its high degree of reproducibility on rechallenge, possible genetic predisposition and mechanisms involving excessive saliuresis and water‐retention. Taken together, the study of Gordon syndrome and TIH may increase understanding of the molecular regulation of sodium trafficking via the thiazide‐sensitive pathway and have important implications for hypertensive patients, both in the identification of new anti‐hypertensive drug targets and avoidance of hyponatraemic side‐effects. This article is protected by copyright. All rights reserved.