Excess dietary salt intake represents a predominant cause of hypertension. However, individual blood pressure response to salt is heterogeneous, possibly due to different inherited susceptibility. The early identification of rare monogenic forms of hypertension associated with abnormalities of renal tubular sodium handling and response to diuretics highlighted the important role of renal alterations in salt-sensitive hypertension. Thereafter, interest has concentrated on the identification of more common allelic variants of candidate genes for hypertension in relation to the salt-sensitivity phenotype. By now, relatively large numbers of such variants have been described, and the pathogenic role of gene-gene interaction has received increasing attention. The alternative approach, consisting of the search for quantitative trait loci in the human genome linked to the transmission of salt-sensitive hypertension, has so far been less successful and cost-effective. This review summarizes consolidated knowledge and discusses the most recent novel findings on the impact of genetic variance on salt-sensitivity of blood pressure.