Shifts in the composition and quantity of microbes within dental plaque biofilms can drive a local proinflammatory immune response state in the epithelial and gingival barrier connective tissues. Infiltrating proinflammatory immune cells within the inflamed connective tissue secrete local factors that induce paracrine signaling to subjacent bone cells. Sustained chronic inflammation disrupts "coupled" osteoclast-osteoblast actions, which ultimately result in alveolar bone destruction.The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism.. Molecular insight into the field of osteoimmunology can lead to novel approaches for the prevention and treatment of diverse inflammatory conditions. As shown by the clinical benefits conferred by anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-6 treatment in RA, osteoimmunological insight is now of obvious importance in clinical applications. Translating these knowledges to periodontal disease in future may benefit the treatment of periodontitis.