Strengthened by promising research data and commercial backing, interest in the field of anti-infective periodontal therapy is rapidly expanding. Management of the periodontal microbiota with antibiotic drugs and antiseptic agents in conjunction with mechanical debridement seems to be more effective than mechanical therapy alone, at least in the treatment of advanced periodontal disease. The choice of a periodontal chemotherapeutic regimen requires an understanding of the usual infecting flora, available antimicrobial agents, and pathogen susceptibility patterns. Systemic administration of combinations of metronidazole and either amoxicillin or ciprofloxacin has been widely used with great success; however the presence of subgingival yeasts and resistant bacteria can be a problem in some periodontitis patients. Valuable antiseptic agents for subgingival application include 10% povidone-iodine for professional use and 0.1-0.5% sodium hypochlorite for patient self-care. These antiseptics have significantly broader spectra of antimicrobial action, are less likely to induce development of resistant bacteria and adverse host reactions, and are considerably less expensive than commercially available antibiotics in controlled release devices. In practice, mechanical debridement combined with subgingival povidone-iodine application in the dental office and sodium hypochlorite irrigation for patient self-care are valuable antimicrobial remedies in the treatment of virtually all types of periodontal disease. Management of moderate to severe periodontitis may require additional systemic antibiotic and/or surgical treatment.