Attempts to control plaque by chemical means using enzymes, antibiotics and antiseptics are reviewed. Enzymes such as mucinase, dehydrated pancreas, enzymes of fungal origin, dextranase and mutanase showed limited clinical success despite promising in vitro and animal studies. Side effects from the use of enzymes were observed. Many antibiotics have been used in attempts to control plaque and several have been successful. However, problems exist from the long-term use of such drugs which precludes their routine use as agents for controlling plaque. The biguanide chlorhexidine is the most widely used and investigated method of chemical plaque control. Many studies have been demonstrated that it will successfully control plaque. No toxic side effects have been reported from its long-term use but local side effects such as staining of the teeth do occur. The quaternary ammonium compounds have at present no advantages over the biguanides and require more frequent usage to achieve the same degree of plaque control as chlorhexidine.