Despite its important role in the control of periodontal disease, mechanical plaque control is not properly practiced by most individuals. Therefore, adjunctive chemical plaque control using chlorhexidine and antibiotics has also been suggested as an additional therapeutic strategy to augment mechanical plaque control. However, the additional effects of adjunctive antibiotic therapy are small, and topical chlorhexidine therapy is not without side effects. Given current limitations, new approaches for the control of biofilm are required. The new therapeutic approaches discussed in this review are divided into two categories: probiotics and vaccines. Probiotics is an interesting new field of periodontology research that aims to achieve biological plaque control by eliminating pathogenic bacteria. In addition, passive immunization using egg yolk antibody raised against periodontal pathogens may be an effective approach for the treatment of periodontitis. Further study to evaluate the possible effects of these biological plaque control methods against periodontal disease is warranted.