The blood pressure response to changes in dietary salt intake is highly variable among individuals and this heterogeneity results from the combined effects of genetic and environmental factors. In recent years, considerable progress has been made in our understanding of the pathogenic mechanisms leading to the development of salt-sensitive hypertension. Much information has come from the investigation of rare monogenic forms of salt-sensitive hypertension and has focused the attention on alterations of renal sodium handling occurring essentially in the distal segments of the nephron. There is now also extending experimental, clinical, genetic and epidemiological evidence suggesting that proximal tubular function is an important determinant of the blood pressure response to salt that would deserve a greater attention.