Antibiotics are critical as an adjunct for treatment of infections. Generally, antibiotics are prescribed systemically. Animal models and clinical studies have clarified the essential role of micro-organisms in the development and perpetuation of pulp and periapical diseases. Studies have also shown that the outcome of treatment of these diseases is dependent on the elimination of micro-organisms from infected root canal systems which is a complicated task. The purpose of this monograph was to explain local applications of antibiotics for treatment of endodontic infections.