Members of the complex family of WRKY transcription factors have been implicated in the regulation of transcriptional reprogramming associated with plant immune responses. Recently genetic evidence directly proving their significance as positive and negative regulators of disease resistance has accumulated. WRKY genes were shown to be functionally connected forming a transcriptional network composed of positive and negative feedback loops and feed-forward modules. Within a web of partially redundant elements some WRKY factors hold central positions mediating fast and efficient activation of defense programs. A key mechanism triggering strong immune responses appears to be based on the inactivation of defense-suppressing WRKY proteins. [13,15,16 ]. Moreover, AtWRKY70 is required for both basal defense and full R-gene (RPP4)-mediated disease resistance against the oomycete Hyaloperonospora parasitica [17 ] Similarly, mutants compromised in AtWRKY33 were more susceptible to infection by B. cinerea and Alternaria brassicicola [18]. Several WRKY factors act as negative regulators of resistance. For instance, basal plant resistance triggered by a virulent P. syringae strain was enhanced in Atwrky7 and Atwrky11/Atwrky17 insertional mutants [19 ,20] thereby also revealing partly redundant functions for these closely related TFs.A small clade (subgroup IIa) of WRKY genes, comprising AtWRKY18, AtWRKY40, and AtWRKY60, play important and partly redundant functions in regulating plant disease resistance. Xu et al. [21 ] showed that Atwrky18/Atwrky40 and Atwrky18/Atwrky60 double mutants were more resistant to P. syringae DC3000 but more susceptible to B. cinerea infection. Atwrky18/Atwrky40 double mutants were also highly resistant toward an otherwise virulent powdery mildew, Golovinomyces orontii [22 ]. In both studies single Atwrky mutants behaved similar to wild-type plants. Interestingly, AtWRKY18 was also identified as a positive regulator required for full SAR, but here AtWRKY40 does not seem to be involved [16 ]. Differences in the experimental set-ups employed by Xu et al.[21 ] and Wang et al.[16 ] may be responsible for the apparent discrepancy observed in the Atwrky18 mutant when challenged by virulent P. syringae strains. Xu et al. used 10-fold higher bacterial inoculum that may have masked the effect on basal resistance caused by loss-ofAtWRKY18 function.In barley, two IIa WRKY members were shown to suppress basal defense to virulent Blumeria graminis in silencing and transient overexpression experiments [22 ,23]. Unfortunately, a solution structure exists only for the common zinc-finger-containing WRKY DNA-binding domain [27 ] and thus no topological information regarding subgroup-specific motifs are available. Nevertheless, some of these structural hallmarks, which appear largely conserved throughout the plant kingdom, have recently been associated with defined molecular or biological functions. It is very likely that they functionally link individual WRKY molecules to each other or to additional de...