WRKY proteins, which contain one or two high conserved WRKYGQK peptide sequence and a zinc finger motif, are a large family of transcription factors (TFs) in plants.There are 74 and 109 WRKY TFs in Arabidopsis and rice, respectively. WRKY TFs regulate expression of genes by binding to W-box in the promoters of the target genes. It has been well documented that WRKY TFs play important roles in plant growth and development, such as lateral root development, senescence, trichome and seed coat development, sugar metabolism, sesquiterpene synthesized and seed germination, and responses to various abiotic and biotic stresses. In this paper, the roles of WRKY TFs in plant stress responses and their regulation mechanism were summarized. Up to now, 10 WRKY TFs have been found to be involved in plant responses against abiotic stresses, including cold, drought, salinity and phosphate starvation, and near 30 WRKY TFs have been reported to function in plant defense against pathogens and herbivores. The WRKY TFs, as positive or negative regulators, can manipulate a lot of processes in plant stress responses by joining the signaling pathways. They may localize upstream or downstream of the signaling pathways, and thus involve in early or late events of the plant stress response. Several WRKY TFs in Arabidopsis and tobacco, for example, AtWRKY53 and AtWRKY33, have been proven to be downstream of MAPK cascades that play important roles in plant development and defense response. Plant can activate hormone signaling pathways when suffered from pathogens or herbivores, and jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) are the three most known defense signal molecules in plants. SA-dependent defense pathway plays a central role in pathogen-induced systemic acquired resistance (SAR) and NPR1 is a key regulator of SAR downstream of SA. In Arabidopsis, rice and tobacco, some WRKY TFs lying upstream or downstream of NPR1 are involved in NPR1-mediated defense responses, and thus regulate plant resistance to pathogen. Induced plant herbivore resistance is mainly related to JA signaling pathway. Two WRKY TFs, NaWRKY3 and NaWRKY6, in tobacco Nicotiana attenuata have been found to regulate herbivore-induced JA levels and the subsequent defense responses, suggesting their important roles in plant defense against herbivores. WRKY TFs may also be regulators for cross-talk between SA- and JA-dependent signal pathways. In Arabidopsis, for example, AtWRKY70 activates SA- but inhibits JA-mediated responses; in contrast, AtWRKY25 and AtWRKY33 have a different role: both of them activate JA- whereas inhibit SA-mediated responses. In addition to the regulation mechanisms stated as above, WRKY TFs can also manipulate the plant stress responses by interacting with other molecules, such as receptor proteins and biochemical enzymes. Moreover, WRKY TFs may be implicated in miRNAs-mediated pathways, which regulate a lot of processes in plant growth and development, and defense responses. Because of a large family, WRKY proteins have been found to have distinct and overlapping functions. Therefore, elucidating how these WRKY proteins regulate the plant defense and how they interact with each other will be hot topics for future studies.