Based on the association of bacterial plaque with the initiation of chronic gingivitis and progression of chronic periodontitis, chemical antiplaque agents have been employed both in prevention of periodontal disease and its treatment. In supragingival plaque control regimens, chlorhexidine has not been superceded as a chemical anti-plaque agent, although other compounds have been shown to be useful. The local side-effects of chlorhexidine and other cationic antiseptics, however, limit their long-term use for prevention. Extrinsic tooth staining in particular remains the greatest problem. Short-term anti-plaque uses for chlorhexidine include as an adjunct to mechanical cleaning in the initial oral hygiene phase of treatment, in situations where mechanical oral hygiene is difficult, including postsurgery, intermaxillary fixation, fixed orthodontic therapy, physically and mentally handicapped individuals, systemic diseases with oral manifestations such as leukaemia. More recent interest in chlorhexidine has resulted from the delivery of compounds subgingivally in the treatment of chronic periodontitis. Such methods have extended the use of chlorhexidine into areas inaccessible to the action of antimicrobial drugs delivered locally by conventional means, such as tooth brushing or mouth rinsing. Available evidence suggests that chlorhexidine may not be as effective as some antimicrobial drugs whose activity is more specific for those organisms considered particularly pathogenic to the periodontal tissues.