Wdreb2, previously isolated as a DREB2 homolog, is expressed in wheat seedlings under abiotic stresses, such as cold, drought, and high salinity, and following treatment with exogenous ABA. In the present study, we generated transgenic tobacco plants expressing Wdreb2 to clarify roles of Wdreb2 in stress tolerance and the direct trans-activation of Cor/Lea genes by WDREB2. Wdreb2 expression significantly improved freezing and osmotic stress tolerance in tobacco plants. Several putative stress- and ABA-responsive cis-elements were found in the 5' upstream regions of four wheat Cor/Lea genes, Wdhn13, Wrab17, Wrab18, and Wrab19. The expression level of a gusA reporter gene under control of Cor/Lea promoter sequences was enhanced by cold, drought and ABA treatment in transgenic tobacco plants. Moreover, the gusA expression level was markedly enhanced by Wdreb2 expression under nonstressful conditions. These results clearly indicate that WDREB2 acts as a transcription factor and positively regulates Wdhn13, Wrab17, Wrab18, and Wrab19 in the development of multiple abiotic stress tolerance in wheat.