Hypertension is the most common disease of the human population. Both genetic and non-genetic factors are involved and high salt intake has been proposed as a major risk factor. According to the hypothesis put forward by Guyton, over 20 years ago, control of blood pressure in the steady-state and on a long-term basis is critically dependent on renal mechanisms (1). During the last decade, a number of genes expressed in the distal part of the nephron have been shown to be directly involved in the control of blood pressure (2). Mutations in single genes that cause isolated Mendelian syndromes characterized by hypertension or hypotension have been identified and, remarkably, these genes have all turned out to be involved in the control of sodium chloride absorption by the distal nephron (Table 1). The distal nephron (Figure 1) is composed of the distal convoluted tubule, the connecting tubule and various segments of the collecting duct. The fact that these are the terminal segments of the nephron affords them the final word, so to speak, on how much salt is excreted. This underlies their critical importance in the maintenance of salt balance, which in turn controls the volume of the extracellular space and blood pressure. The reabsorption of sodium in the distal tubule and the collecting tubules is closely regulated, chiefly by the action of the hormone aldosterone.