AbstractPeriodontitis is a common chronic inflammatory disease characterized by destruction of the supporting structures of the teeth. Severe periodontitis is highly prevalent—affecting 10%‐15% of adults—and carries several negative comorbidities, thus reducing quality of life. Although a clear relationship exists between severity of obesity and incidence of periodontal disease, the biologic mechanisms that support this link are incompletely understood. In this conceptual appraisal, a new “two‐hit” model is presented to explain obesity‐exacerbated periodontal bone loss. This proposed model recognizes a previously unappreciated aspect of myeloid‐derived suppressor cell population expansion, differentiation, and activity that can participate directly in periodontal bone loss, providing new mechanistic and translational perspectives.