CBF/DREB1 (C-repeat-binding factor dehydration responsive element-binding factor 1) genes encode a small family of transcriptional activators that have been described as playing an important role in freezing tolerance and cold acclimation of plants. However, their role on responding to biotic stress such as disease resistance has not been described. We here report that CBF1 and CBF2 genes also play an important role in early response to the pathogen infection of grapevine downy mildew (DM) disease. An expression analysis indicated that the expression level of CBF1 and CBF2 increased dramatically and reached a peak at 7 h after infection in a highly resistant a grapevine, which was much faster and lot more dramatic than moderate resistant and susceptible ones. When the CBF2 cloned from the DM resistant grapevine was transformed to downy mildew susceptible Arabidopsis COL0, the transgenic lines showed an increased resistance to downy mildew disease. Pathogen related proteins (PR1, PR4, PR5, PDF1.2) were identified to be 1.5-6 fold higher in the transgenic Arabidopsis lines. It appeared that CBF/DREB1 plays a role in increasing resistance to downy mildew disease by upregulating downstream PR proteins.