High salt concentration represents one of the most significant abiotic constraints, affecting all life forms including plants and cyanobacteria. Soil salinity curtails plant growth by way of osmotic, ionic and oxidative stresses resulting in multiple inhibitory effects on various physiological processes such as growth, photosynthesis, respiration and cellular metabolism. In order to combat high salinity, various adaptive strategies employed include ion homeostasis achieved by ion transport and compartmentalization of injurious ions, osmotic homeostasis by accumulation of compatible solutes/osmolytes and upregulation of antioxidant defence mechanism. The aforesaid processes are executed through SOS and MAPK signalling pathways leading to modulation of gene expression. Salt stress signal transduction pathways initiate through sensing extracellular Na + ions causing modification of constitutively expressed transcription factors. This modification is responsible for expression of early transcriptional activators such as CBF/DREB gene family which eventually activate stress tolerance effector genes such as osmolyte biosynthesis genes, detoxification enzymes, and chaperones. Various genes/cDNAs encoding proteins involved in these adaptive mechanisms have been isolated and identified. Bioinformatic predictions through docking revealed interaction of salt across the species at conserved domains and motifs as a possible mechanism for response of a particular protein under salt stress. In this chapter, major aspects of salt stress are reviewed with emphasis on its detrimental consequences and biochemical and molecular mechanisms of signal transduction in plants and cyanobacteria under high salinity.