The grain yield of a crop represents the expression of many thousands of genes integrated over the life of each of the component plants in the crop in response to environment, as well as severely affected by parasite, including pest and pathogen. Plant has no capacity to elude parasite other than by altering intrinsic gene expression or gene combinations to improve performance under pathogen. Transcriptional control is a crucial part of genes expression, especially in plant response to a range of stresses. Wheat (Triticum aestivum L.) is one of the most important cultivated crops, while its production isseverely affected by stripe rust and powdery mildew. Unfortunately, coupled with the loss of genetic diversity in wheat breeding programs, the disease resistance germplasms are more and more scarce due to the frequently variation of epidemic virulent race. Research carried out in the past few years has been productive in identifying TFs for regulating resistance to pathogen stress in wheat and other plant species. The increasing studies showed that Transcription Factors (TFs) are potent positive, negative, cis-and trans-regulators activating the functional gene. Herein, we highlighted the recent progress in elucidating the roles of TFs in wheat defense against pathogen, as well as the potential relationship between transcription factors family with regulating pathogen type, although there should be no expectation that everlasting favorable genes performance will be discovered for variable environments. Furthermore, we discussed new ways to improve varieties' resistance using biotechnology combining with empirical breeding program. This leads to new ideas to enhance wheat resistance or tolerance to disease in virtue of the progress of wheat genetic engineering. This maybe a new way to improve adaptive plasticity of wheat in highly variable environments as aresult of introducing greater diversity of resistance gene pool to cropping systems.