Soil salinity is among the leading environmental stresses affecting global agriculture, causing billions of dollars in crop damages every year. Regardless of the cause, ion toxicity, water deficit, or nutritional imbalance, high salinity in the root zone severely impedes normal plant growth and development, resulting in reduced crop productivity or crop failure. Development of salt-tolerant cultivars is an attractive and economical approach to solving this problem. Although several salt-tolerant plant genotypes have been developed through transgenic approaches, often they have failed or exhibited limited success under field saline conditions. This is due to several reasons, including the fact that plant growth and development under saline conditions in the field is often influenced by cumulative effects of multiple environmental stresses and genetic factors, which may not have been considered during the development of salt-tolerant transgenic plants. Adoption of inappropriate screening techniques or selection criteria may also lead to selection of genotypes that may not be stress tolerant in a real sense. In most plant species, salt tolerance is a genetically complex trait, often modulated by multiple biosynthetic and signaling pathways. Cross-talks among various stress-controlling pathways have been observed under salt stress, many of which are regulated by transcription factors. Thus, a comprehensive knowledge of the up- and downregulating genes under salt-stress is necessary, which would provide a better understanding of the interactions among pathways in response to salt stress. Attaining such knowledge is a good step toward successful development of salt-tolerant crop cultivars. To this end, DNA microarray technology has been employed to study expression profiles in different plant species and at varying developmental stages in response to salt stress. As a result, large-scale gene expression profiles under salt stress are now available for many plant species, including Arabidopsis, rice, barley, and ice plant. Examinations of such gene expression profiles will help understand the complex regulatory pathways affecting plant salt tolerance and potentially functional characterization of unknown genes, which may be good candidates for developing plants with field salt tolerance. In this article, we review and discuss the current knowledge of plant salt tolerance and the extent to which expression profiling has helped, or will help, a better understanding of the genetic basis of plant salt tolerance. We also discuss possible approaches to improving plant salt tolerance using various tools of biotechnology.