BACKGROUND:Plant pathogens are responsible for many of history’s greatest famines.Understanding how plants defend themselves against pathogens is crucial to preventing future famines.Salicylic acid (SA)-mediated plant defense is a key defense pathway,which plants use to defend against biotrophic and hemi-biotrophic pathogens.As a master regulator of SAmediated plant defense,NPR1 interacts with TGA and WRKY transcription factor families,individual members of which positively or negatively regulate plant defense.OBJECTIVE:In this review we describe the recent developments and predict future directions of research on the involvement of circadian rhythm-,autophagy-,and viral RNA silencing-related genes in SA-mediated plant defense on SA,on plant defense,the induction effects of PR proteins,and the mechanisms by which NPR1 regulates defense-related genes.METHODS:We performed an extensive search of current and past literature using the PubMed,Google Scholar,and Google search engines.Our search terms included:SA-mediated plant defense, and NPR1 [AND] salicylic acid. Other search terms,wildcards,and Boolean operators were paired with NPR1 or plant defense as needed to research more detailed information related to specific topics covered within this review.We also used Google to search for,economic impact citrus greening, aspirin, Irish potato famine, and rice blast, among other terms,to gather background information on the history and impact of plant diseases,and the historical use of aspirin.RESULTS:Of 148 sources found,132 were directly related to plant defense.The remaining sources are related to the historical and economic impact of plant diseases and the historical use and mechanism of action of aspirin or salicylate.All reviewed sources have been documented in the references section.CONCLUSION:The topic of salicylic acid-mediated plant defense is broad,and new research is expanding our understanding of this topic quickly.In this review,we give a basic overview of the historical economic impact of plant diseases,and how an understanding of SA-mediated plant defense can prevent future famines.We provide a basic overview of plant defense,then discuss how SA acts as a defense signaling molecule.We discuss how SA regulates NPR1,which goes on to activate expression of SA-related genes including PR genes.Later,we discuss current research topics,including the role of NPR1 and SA in autophagy,circadian rhythmicity,viral gene silencing,SA biosynthesis,and SAR.We also discuss the potential roles of PR proteins,other SA binding proteins,WRKY and TGA family transcription factors,Elongator,and ER transport proteins in plant defense.Finally,we discuss the potential future routes that research into this topic could take,in order to further our understanding of role SA plays in plant defense.