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 SOS1, 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 QTL in monocot crop plants are also based on this HKT-mediated mechanism. Sodium toxicity and salt tolerance in plants Physiological studies have shown that salinity stress in plants is multifactorial, including osmotic stress [1] and cellular sodium (Na + ) toxicity, such as inhibition of vital enzymes and metabolic processes [2][3][4][5][6][7][8][9][10][11][12][13][14]. Photosynthetic processes are among the most sensitive to salinity and, therefore, salinity stress directly reduces carbon fixation and biomass production in plants [5,[15][16][17][18]. Sodium transport processes have major roles in salinity tolerance, including organellar Na + sequestration [4,8,9,15,19,20]; Na + extrusion by plasma membrane Na + -H + exchange transporters, such as AtSOS1 [21,22] and exclusion of Na + from leaves and shoots [11,[23][24][25][26][27][28][29]. In addition, reducing Na + uptake or increasing cytoplasmic potassium (K + ) levels relative to Na + increases Na + tolerance in plants [30][31][32][33]. However, given that multiple independent cationic nutrient uptake transporters mediate Na + uptake from the soil into roots (reviewed in Refs [6,34]), engineering of reduced Na + influx into plant roots is likely a more challenging endeavor. The identification and characterization of Na + -permeable transporters is therefore pivotal to understanding plant Na + toxicity and tolerance [13,[35][36][37][38].Recent research has demonstrated that members of the high-affinity K + transporter (HKT) transporter/channel family mediate important Na + tolerance mechanisms in plants. The TaHKT2;1 gene from wheat (Triticum aestivum) (previously named HKT1), was the first HKT transporter gene found in plants [39]. It was shown to mediate high-affinity Na + -K + cotransport and also preferred Na + -selective low-affinity Na + transport in the presence of a Corresponding author: Horie, T. (horie@rib.okayama-u.ac.jp). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please ...