Specific pathogenic bacteria play a central role in the etiology and pathogenesis of destructive periodontal disease. Under suitable conditions, periodontal pathogens colonize the subgingival environment and are incorporated into a tenacious biofilm. Successful prevention and treatment of periodontitis is contingent on effective control of the periodontopathic bacteria, which is accomplished with professional treatment of diseased periodontal sites and patient performed plaque control. Subgingival mechanical debridement, with or without surgery, constitutes the basic means of disrupting the subgingival biofilm and controlling pathogens. Appropriate antimicrobial agents that can be administered systemically or via local delivery may enhance eradication or suppression of subgingival pathogens. Microbiological testing may aid the clinician in the selection of the most effective antimicrobial agent or combination of agents. Understanding the benefits and limitations of antibiotics and antiseptics will optimize their usefulness in combating periodontal infections.