High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy, and stroke incidence. In this review we discuss the molecular origins of primary sensors involved in the phenomenon of salt sensitivity. Based upon the analysis of literature data we conclude that the kidneys and the central nervous system (CNS) are two major sites for salt sensing via several distinct mechanisms: (i) [Cl^-] sensing in renal tubular fluids primarily by the NKCC2B and NKCC2A isoforms of Na⁺,K⁺,Cl^- cotransporter, whose expression is mainly limited to macula densa cells, (ii) [Na⁺] sensing in cerebrospinal fluid (CSF) by a novel isoform of Na⁺ channels, Nax, expressed in subfornical organs, (iii) sensing of the CSF osmolality by the mechanosensitive, non-selective cation channels, Trpv1, expressed in neuronal cells of the supraoptic and paraventricular nuclei, and (iv) osmolarity sensing by volume-regulated anion channels in glial cells of the supraoptic and paraventricular nuclei. Such multiplicity of salt-sensing mechanisms likely explains the differential effects of Na⁺ and Cl^- loading on the long-term maintenance of elevated blood pressure that is documented in experimental models of salt-sensitive hypertension.