The salinization of irrigated lands is increasingly detrimental to plant biomass production and agricultural productivity, as most plant species are sensitive to high concentrations of sodium (Na(+)), which causes combined Na(+) toxicity and osmotic stress. Plants have multiple Na(+)-transport systems to circumvent Na(+) toxicity. Essential physiological functions of major Na(+) transporters and their mechanisms mediating salinity resistance have been identified in Arabidopsis , including the AtSOS1, AtNHX and AtHKT1;1 transporters. As we discuss here, recent studies have demonstrated that a class of xylem-parenchyma-expressed Na(+)-permeable plant HKT transporters represent a primary mechanism mediating salt tolerance and Na(+) exclusion from leaves in Arabidopsis, and that major salt-tolerance quantitative trait loci in monocot crop plants are also based on this HKT-mediated mechanism.