That chronic periodontitis is an infectious disease is now firmly established, and the primary role of Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola is generally accepted. Treatment by mechanical means such as scaling and root planing or surgery generally results in significant clinical improvement but may not arrest the progress or recurrence of disease. Several studies have shown that the probability of achieving lasting stability as measured by the arrest of progressive attachment loss and bone loss by primary mechanical therapy is a function, in major part, of whether pathogenic microorganisms are still present at local subgingival sites at the completion of active therapy. The infecting bacterial species are susceptible to killing by several antibiotics including, among others, tetracycline-class drugs, amoxicillin and metronidazole as well as by local exposure to chlorhexidine. Randomized clinical trials have shown that use of systemically administered antibiotics as an adjunct to mechanical therapies significantly enhances clinical outcomes and stability. Several slow-release devices that deliver anti-microbial drugs directly into periodontal pockets have been developed and are now on the market. Use of these devices permits local delivery of long-lasting, high concentrations of doxycycline (Atridox) minocycline (Arestin), and chlorhexidine (PerioChip) directly into periodontal pockets. Although these devices differ with regard to ease of use, concentration of drug delivered and length of time high drug concentrations can be maintained, randomized clinical trials have shown that their use as an adjunctive treatment to scaling and root planing results in a significantly greater reduction of periodontal pocket depth and an average increase in clinical periodontal attachment level of about 0.8 mm. Gain in clinical attachment is greater in deeper pockets than in shallower pockets. Locally delivered adjunctive anti-microbial therapy is an effective means to enhance therapeutic outcomes.