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By priming the plant\u2019s innate immune system, these compounds can induce disease resistance against a broad spectrum of pathogens without directly inhibiting their proliferation. Key advantages of plant activators include prolonged defense activity, lower effective dosages, and negligible risk of pathogen resistance development. Among the various defensive pathways targeted, the salicylic acid (SA) signaling cascade has been extensively explored, leading to the successful development of commercial activators of systemic acquired resistance, such as benzothiadiazole, for widespread application in crop protection. While the action sites of many SA-targeting activators have been preliminarily mapped to different steps along the pathway, a comprehensive understanding of their precise mechanisms remains elusive. This review provides a historical perspective on plant activator development and outlines diverse screening strategies employed, from whole-plant bioassays to molecular and transgenic approaches. We elaborate on the various components, biological significance, and regulatory circuits governing the SA pathway while critically examining the structural features, bioactivities, and proposed modes of action of classical activators such as benzothiadiazole derivatives, salicylic acid analogs, and other small molecules. Insights from field trials assessing the practical applicability of such activators are also discussed. Furthermore, we highlight the current status, challenges, and future prospects in the realm of SA-targeting activator development globally, with a focus on recent endeavors in China. Collectively, this comprehensive review aims to describe existing knowledge and provide a roadmap for future research toward developing more potent plant activators that enhance crop health.<\/jats:p>","DOI":"10.3390\/genes15091237","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"1237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Past, Present, and Future of Plant Activators Targeting the Salicylic Acid Signaling Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-3259","authenticated-orcid":false,"given":"Misbah","family":"Naz","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangcen","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-5902","authenticated-orcid":false,"given":"Nazeer","family":"Ahmed","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Forestry, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7130-8457","authenticated-orcid":false,"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature05286","article-title":"The plant immune system","volume":"444","author":"Jones","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev.phyto.42.040803.140421","article-title":"Systemic acquired resistance","volume":"42","author":"Durrant","year":"2004","journal-title":"Annu. 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