This article reviews the studies that provided the safety and efficacy data essential for the Food and Drug Administration approval of Atridox. These studies detail the clinical effectiveness of Atridox and provide the foundation for an understanding of the use of Atridox in the clinical management of patients with periodontitis. Atridox is a locally delivered, controlled-release system for the administration of high concentrations of doxycycline to the periodontal pocket. Nine-month clinical studies involving more than 800 patients have shown Atridox and scaling and root planing to be superior to placebo and oral hygiene for the efficacy parameters of attachment level, probing depth, and bleeding on probing. The positive clinical effects are consistent throughout a wide range of patients with varied histories of periodontal therapy. The implications of these findings as they relate to clinical practice are briefly addressed.