Functional analyses of MADS-box transcription factors in plants have unraveled their role in major developmental programs (e.g; flowering and floral organ identity), as well as in stress-related developmental processes such as abscission, fruit ripening and senescence. Over-expression of the OsMADS26 gene in rice (Oryza sativa) has revealed a possible function related to stress response (Lee et al., 2008b). Here we show that OsMADS26 down-regulated plants exhibit enhanced resistance against two major rice pathogens, Magnaporthe oryzae and Xanthomonas oryzae. Despite this enhanced resistance to biotic stresses, OsMADS26 down-regulated plants also displayed enhanced tolerance to water deficit. These phenotypes were observed both in controlled and field conditions. Interestingly, alteration of OsMADS26 expression has no strong impact on plant development. Gene expression profiling revealed that a majority of genes miss-regulated in over-expresser and down-regulated OsMADS26 lines compared to control plants are associated to biotic or abiotic stress response. Altogether, our data indicate that OsMADS26 acts as an upstream regulator of stress-associated genes and thereby as a hub to modulate the response to various stresses in the rice plant.