In field conditions, crops are adversely affected by a wide range of abiotic stresses including drought, cold, salt, and heat, as well as biotic stresses including pests and pathogens. These stresses can have a marked effect on crop yield. The present and future effects of climate change necessitate the improvement of crop stress tolerance. Plants have evolved sophisticated stress response strategies, and genes that encode transcription factors (TFs) that are master regulators of stress-responsive genes are excellent candidates for crop improvement. Related examples in recent studies include TF gene modulation and overexpression approaches in crop species to enhance stress tolerance. However, much remains to be discovered about the diverse plant TFs. Of the >80 TF families, only a few, such as NAC, MYB, WRKY, bZIP, and ERF/DREB, with vital roles in abiotic and biotic stress responses have been intensively studied. Moreover, although significant progress has been made in deciphering the roles of TFs in important cereal crops, fewer TF genes have been elucidated in sorghum. As a model drought-tolerant crop, sorghum research warrants further focus. This review summarizes recent progress on major TF families associated with abiotic and biotic stress tolerance and their potential for crop improvement, particularly in sorghum. Other TF families and non-coding RNAs that regulate gene expression are discussed briefly. Despite the emphasis on sorghum, numerous examples from wheat, rice, maize, and barley are included. Collectively, the aim of this review is to illustrate the potential application of TF genes for stress tolerance improvement and the engineering of resistant crops, with an emphasis on sorghum.

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