Osteoimmunology describes the cross-talk of cells of the musculoskeletal and the immune system during the pathogenesis of various diseases; among the most prevalent ones is periodontitis, a chronic infectious inflammatory disease of the tooth-supporting structures, i.e., the periodontium consisting of the gingiva, alveolar bone, periodontal ligament, and root cementum. Periodontal disease is initiated by oral pathogens that accumulate at the gingival margin of the teeth and thereby trigger a response of the innate and adaptive immunity. In contrast to other osteoimmunological disorders (e.g., osteoporosis, rheumatoid arthritis), the immune system plays a two-sided role in the pathogenesis of periodontitis: it controls the infection and protects the organism from bacterial invasion but also propagates the destruction of the soft and hard tissues surrounding the tooth. Periodontitis, if left untreated, finally results in tooth loss.