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The systemic administration of antibiotics in conjunction with mechanical biofilm disruption results in reduced numbers of subgingival periodontal pathogens and improved clinical outcomes. Penicillins, tetracyclines, macrolides, quinolones, and nitroimidazoles were used in laboratory and clinical studies. The current literature was reviewed and studies investigating the effect of antibiotics on periodontal pathogens in biofilm models or in clinical trials were analyzed. While there is only a limited number of in vitro studies, numerous