Among abiotic stresses, high salinity stress is the most severe environmental stress, which impairs crop production on at least 20% of irrigated land worldwide. In response to high salinity stress, various genes get upregulated, the products of which are involved either directly or indirectly in plant protection. Some of the genes encoding osmolytes, ion channels, receptors, components of calcium signaling, and some other regulatory signaling factors or enzymes are able to confer salinity-tolerant phenotypes when transferred to sensitive plants. Overall, the susceptibility or tolerance to high salinity stress in plants is a coordinated action of multiple stress responsive genes, which also cross talk with other components of stress signal transduction pathways. High salinity exerts its negative impact mainly by disrupting the ionic and osmotic equilibrium of the cell. In saline soils, high levels of sodium ions lead to plant growth inhibition and even death; therefore, mechanisms of salinity tolerance involve sequestration of Na(+) and Cl(-) in vacuoles of the cells, blocking of Na(+) entry into the cell, Na(+) exclusion from the transpiration stream, and some other mechanisms that help in salinity tolerance. Understanding these mechanisms of stress tolerance, along with a plethora of genes involved in the stress signaling network, is important to improve high salinity stress tolerance in crops plants. This chapter first describes the adverse effect of salinity stress and general pathway for the plant stress response, followed by roles of various ion pumps, calcium, SOS pathways, ABA, transcription factors, mitogen-activated protein kinases, glycine betaine, proline, reactive oxygen species, and DEAD-box helicases in salinity stress tolerance. The cross-tolerance between stresses is also mentioned.