The molecular characterization of rare monogenic salt-sensitive forms of hypertension has focused the attention on alterations of renal sodium handling occurring essentially in the distal nephron where sodium excretion is finely tuned to maintain sodium balance. These observations however only partly explain the mechanisms of the blood pressure response to changes in sodium intake observed in patients with essentially hypertension. In fact, there is growing experimental, clinical, genetic, and epidemiological evidence that proximal tubular sodium reabsorption is also an important determinant of blood pressure control in humans. Thus, we have observed important differences in renal tubular sodium handling and particularly in proximal sodium reabsorption depending on race and on the genetic background Considering the actual level of evidence, segmental renal sodium handling should perhaps be investigated more frequently in the future. But to generate a greater interest for this type of research, new techniques should be developed enabling to assess reliably the renal tubular response to sodium in humans. A better characterization of the molecular mechanisms whereby renal tubules adapt to changes in sodium intake would certainly improve our understanding of the role of the kidney in mediating salt sensitivity in hypertension and diseases such as obesity and diabetes.