Periodontitis is characterized by a general inflammation of the tooth-supporting tissues, which leads to apical migration of the junctional epithelium along the root surface and progressive destruction of the periodontal ligament and the alveolar bone. Although the bacteria present within the subgingival dental biofilm constitute the primary etiologic agents of periodontitis, the host's immune response modulates development of the condition toward either destruction or healing. Given the infectious nature of periodontal diseases and the limited results with conventional mechanical therapies for the treatment of certain forms of periodontitis (aggressive and refractory), the use of antibiotics is warranted in certain cases. This article provides an update on systemic antibiotic therapy for the treatment of periodontitis.