Abiotic stresses impair crop production on irrigated land worldwide. Overall, the susceptibility or tolerance to the stress in plants is a coordinated action of multiple stress responsive genes, which also cross-talk with other components of stress signal transduction pathways. Plant responses to abiotic stress can be determined by the severity of the stress and by the metabolic status of the plant. Abscisic acid (ABA) is a phytohormone critical for plant growth and development and plays an important role in integrating various stress signals and controlling downstream stress responses. Plants have to adjust ABA levels constantly in response to changing physiological, metabolic and environmental conditions. To date, the mechanisms for fine-tuning of ABA levels remain elusive. The mechanisms by which plants respond to abiotic stresses include both ABA-dependent and ABA-independent processes. Various transcription factors such as DREB2A/2B, AREB1, RD22BP1 and MYC/MYB are known to regulate the ABA-responsive gene expression by interacting with their corresponding cis-acting elements such as DRE/CRT, ABRE, and MYCRS/MYBRS, respectively. Due to polygenic nature of the trait, it is becoming important to apply genome wide tools for precise understanding of the mechanisms and to ultimately improve stress tolerance in crops plants. This chapter describes the ABA-induced stress response pathway and the application of ‘omics’ technologies to unravel the complex mechanisms governing abiotic stress tolerance in plants.