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The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma. On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm. The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance. Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases. Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation. Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset. In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option. Inadequate oral hygiene and tobacco smoking are contra-indications to the use of antimicrobials. The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established. The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned.