The detection and quantitation of immune responses to infections have long been used as a diagnostic tool in medical infections. Recently, increasing evidence has supported that active, specific antibody responses to selected members of the subgingival microbiota are noted in periodontitis patients. This report describes the various specificities of this antibody as they relate to periodontitis classification and prognosis. The functional aspects of the serum antibody have come under increasing scrutiny to understand better the potential immunologic mechanisms acting in the periodontium. Data are available that describe opsonizing potential, complement fixing ability, blocking functions, and anti-toxic capacity for the antibody. Longitudinal alterations in specific antibody levels are shown to relate to infection and accompany changes in the burden of a specific microorganism in the subgingival plaque. Thus, these antibody changes could be useful indicators of altered host-parasite interactions that presage a disease-active episode. Finally, studies were designed to examine the ability of antibody to reflect the effects of treatment on the disease. The results indicated that specific antibody levels change with mechanical, antimicrobial, and anti-inflammatory treatments. The findings described in this report suggest that evaluation of the level and specificity of serum antibody can be a beneficial adjunct in designing and implementing clinical studies delineating the initiation, progression, and treatment of periodontitis.