Crop plants should be resilient to climatic factors in order to feed ever-increasing populations. Plants have developed stress-responsive mechanisms by changing their metabolic pathways and switching the stress-responsive genes. The discovery of plant transcriptional factors (TFs) as key regulators of different biotic and abiotic stresses have opened up new horizons for plant scientists. TFs perceive the signal and switch certain stress-responsive genes on and off by binding to different cis-regulatory elements. The above 50 species of plant TFs have been reported in nature. DREB, bZIP, MYB, NAC, Zinc-finger, HSF, Dof, WRKY, and NF-Y are important with respect to biotic and abiotic stresses whereas the role of many TFs is yet to explore. In this review, we summarize the role of different stress-responsive TFs with respect to biotic and abiotic stresses. Further, challenges and future opportunities linked with TFs for developing climate-resilient crops are also elaborated.