Recent interest in the control and modulation of periodontal disease has focused on the potential benefits of blocking the host response mechanisms involved in the progression of the disease. In addition to recent advances in the identification and control of etiologic bacteria, investigators have indicated promising results using nonsteroidal antiinflammatory drugs (NSAIDs) as inhibitors of the inflammatory destruction in periodontal disease. This article examines research efforts over the last 20 years describing the role of prostaglandins in periodontal disease and the effect of NSAIDs on the progression of gingival inflammation and alveolar bone loss.