Over the last 100 years, methods of surgical periodontal treatment have enjoyed a history of success in improving oral health. The paradigm of care is based on the "non-specific plaque hypothesis"-that is, the overgrowth of bacterial plaques cause periodontal disease, and the suppression of this overgrowth reduces disease risk. The central feature of this approach to care is the removal of inflamed gingival tissue around the teeth to reduce periodontal pocket depth, thereby facilitating plaque removal by the dentist and by the patient at home. Over the last 30 years, with the recognition that periodontal disease(s) is caused by specific bacteria and that specific antimicrobial agents can reduce or eliminate the infection, a second paradigm has developed. This new paradigm, the "specific plaque hypothesis", focuses on reducing the specific bacteria that cause periodontal attachment loss. The contrast between the two paradigms can be succinctly stated as follows: The antimicrobial therapy reduces the cause, while the surgical therapy reduces the result of the periodontal infection. The specific plaque hypothesis has two important implications. First, with the increasing attention to evidence-based models for prevention, treatment, outcome assessment, and reimbursement of care, increasing attention and financial effort will be channeled into effective preventive and treatment methods. Second, the recent observations that periodontal infections increase the risk of specific systemic health problems, such as cardiovascular disease, argue for the prevention and elimination of these periodontal infections. This review highlights some of the evidence for the specific plaque hypothesis, and the questions that should be addressed if antimicrobial agents are to be used responsively and effectively.