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 ef‐ fects 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 tol‐ erance 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 bind‐ ing 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.