Periodontal disease involves inflammation of the gingival tissues, caused by microbial pathogens. Recent papers suggest that emotional stress worsens periodontal disease. Here we review the literature and propose that corticotropin-releasing hormone (CRH) secreted under stress stimulates gingival mast cells together with other neuropeptides and cytokines to secrete pro-inflammatory molecules that contribute to periodontal pathology. Stress reduction and/or mast cell inhibition may provide additional therapeutic approaches.