Periodontitis is a result of an infection with specific pathogenic microorganisms. Thus, the local delivery of antimicrobials has been investigated as a possible method for controlling this infection and treating periodontal disease. A number of antimicrobial agents have been studied both as adjunctive therapies with scaling and root planing and as stand-alone chemotherapies. These agents have been administered in irrigation solutions and as single-dose formulations, but with little long-term efficacy in the treatment of periodontitis. Recent investigations have focused on the delivery of antimicrobials in sustained-release formulations designed to maintain effective concentrations of drug within the periodontal pocket. This article provides an overview of the development of the use of locally delivered antimicrobials in periodontal therapy and the current state-of-the-art of the technique.