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Historically, the therapeutic approach to periodontitis has concentrated on local intervention within periodontal pockets. Local drug delivery systems show potential for targeting periodontal infections with high drug concentrations while minimizing systemic side effects. This could potentially help overcome the challenges posed by microbial biofilms. However, evidence suggests that periodontitis is not a disease affecting only confined areas of a dentition. Currently, in the presence of multiple deep pockets, local therapy is less cost\u2010effective than systemic antibiotics due to the costs of products and the extensive professional chair time required for their application. Isolated deep pockets in otherwise stable dentitions are often caused by problems that cannot be resolved with antimicrobial agents. Finally, recurrent biofilm formation in residual pockets during the maintenance phase can be addressed through suitable physical rather than chemical procedures.<\/jats:p>","DOI":"10.1111\/prd.12630","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T08:39:15Z","timestamp":1748507955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mystery and misery of locally\u2010delivered drug therapy in periodontics. Historical concepts and current state"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3386-8503","authenticated-orcid":false,"given":"Andrea","family":"Mombelli","sequence":"first","affiliation":[{"name":"Division of Regenerative Dental Medicine and Periodontology University Clinics of Dental Medicine, University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-8958","authenticated-orcid":false,"given":"Alkisti","family":"Zekeridou","sequence":"additional","affiliation":[{"name":"Division of Regenerative Dental Medicine and Periodontology University Clinics of Dental Medicine, University of Geneva  Geneva 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