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The objective of this study was to optimize a periodontal drug delivery system containing antibacterial drugs having synergistic activity for the treatment of mixed periodontal infections. Periodontal pockets provide natural reservoir bathed by gingival crevicular fluid that is easily accessible for the insertion of a delivery device. Controlled release delivery of antimicrobials directly into periodontal pockets has received great interest and appears to hold a sound promise in periodontal therapy. Both topical drug delivery and controlled drug release have been termed as local drug delivery. It does not substitute the local instrumentation but acts as an adjunct to it. The periodic use of local drug delivery in minimizing bleeding, stabilizing attachment levels and thereby reducing probing depth, would allow better control and management of periodontal disease. Various drugs have been under investigation for more than 3 decades promising encouraging results. The rationales of using antibacterial drugs through local delivery into the periodontal pockets have been discussed.