Periodontitis is a biofilm infection with a mixed microbial aetiology. Periodontitis is generally treated by non-surgical mechanical debridement and regular periodontal maintenance care. Periodontal surgery may be indicated for some patients to improve access to the root surface for mechanical debridement. A range of systemic antibiotics for treatment of periodontitis has been documented, with some studies showing superior clinical outcomes following adjunctive antibiotics while others do not. This has resulted in controversy as to the role of systemic antibiotics in the treatment of periodontal diseases. Recent systematic reviews have provided an evidence-based assessment of the possible benefits of adjunctive antibiotics in periodontal therapy. This review aims to provide an update on clinical issues of when and how to prescribe systemic antibiotics in periodontal therapy.