During the last 50 years, it has been shown that abiotic stresses influence plant growth and crop production greatly, and crop yields have evidently stagnated or decreased in economically important crops, where only high inputs assure high yields. The recent manifesting effects of climate change are considered to have aggravated the negative effects of abiotic stresses on plant productivity. On the other hand, the complexity of plant mechanisms controlling important traits and the limited availability of germplasm for tolerance to certain stresses have restricted genetic advances in major crops for increased yields or for improved other traits. However, some level of success has been achieved in understanding crop tolerance to abiotic stresses; for instance, identification of abscisic acid (ABA) receptors (e.g., ABA-responsive element (ABRE) binding protein/ABRE binding factor (AREB/ABF) transcription factors), and other regulons (e.g., WRKYs, MYB/ MYCs, NACs, HSFs, bZIPs and nuclear factor-Y (NF-Y)), has shown potential promise to improve plant tolerance to abiotic stresses. Apart from these major regulons, studies on the post-transcriptional regulation of stress-responsive genes have provided additional opportunities for addressing the molecular basis of cellular stress responses in plants. This chapter focuses on the progress in the study of plant tolerance to abiotic stresses, and describes the major tolerance pathways and implicated signaling factors that have been identified, so far. To link basic and applied research, genes and proteins that play functional roles in mitigating abiotic stress damage are summarized and discussed.In the past 100 years, conventional breeding ( Figure 2; based on observed variation and controlled mating) approaches have randomly exploited these plant tolerance mechanisms with limited success. Moreover, in vitro induced variations have also shown little progress in the improvement of plants against abiotic stresses. These conventional breeding approaches are limited by the complexity of stress tolerance traits coupled with less genetic Plant Genomics 168 variation exhibited by most crops due to domestication bottlenecks. The recent reports that the cultivated gene pool of major cereal crops, e.g., rice, maize and wheat, has reduced in genetic variation compared to wild relatives [10-12], raises concern, and could probably undermine the current efforts to identify genetic sources of resistance within the cultivated genepools. It is important, therefore, to consider exploring alternative sources of resistance by incorporating modern techniques into traditional breeding strategies to develop stresstolerant crops (Figure 2).Recently, with the support of genomics, targeted genetic studies involving QTL mapping and validation, identification of key regulatory genes, e.g., genes encoding for ABA receptors, developments in transcriptional and post-transcriptional regulation of stress-responsive genes and studies on hormonal interactions during plant response to stress, have provided opp...