Periodontitis is a multifactorial disease of polymicrobial infections. The main etiologic factors implicated in the development of Periodontitis include the gramnegative, anaerobic or Microaerophilic bacteria within the biofilm. The microbial challenge consisting of antigens, lipopolysaccharides, and other factors which result in the development of gingivitis or the initiation of the Periodontitis. Neutrophils, production of protective antibodies, and possibly the release of antiin?ammatory cytokines including transforming growth factor-? (TGF-?), interleukin-4 (IL-4), IL-10, and IL-12. Hostmodulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, nitrous oxide (NO) synthase inhibitors, recombinant human interleukin-11 (rhIL-11), omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA), mitogen-activated protein kinase (MAPK) inhibitors, nuclear factor-kappa B (NF-kb) inhibitors, osteoprotegerin, and tumor necrosis factor antagonist are some of the therapeutic agents that have host modulating properties.