The article discusses the recent understanding of the pathogenesis of periodontitis, a chronic inflammatory disease affecting the supporting structures of teeth. Recent studies have revealed that the breakdown of host-microbe homeostasis can lead to dysbiosis and periodontitis in susceptible hosts. Keystone pathogens, such as *P. gingivalis*, and pathobionts, which are normally harmless commensals, exhibit synergistic interactions that enhance their colonization and persistence in an inflammatory environment, leading to tissue destruction and bone loss. The dysbiotic microbial communities thrive by exploiting tissue-destructive inflammation, creating a self-feeding cycle of escalating dysbiosis and inflammatory bone loss. The article highlights the role of host susceptibility, including immunodeficiencies, systemic diseases, and environmental factors, in the development of periodontitis. It also explores the cellular and molecular mechanisms involved in periodontal inflammation and bone loss, particularly the involvement of neutrophils, Th17 cells, and regulatory T cells. Finally, the article discusses therapeutic strategies targeting host signaling pathways to manage periodontitis, emphasizing the importance of inhibiting inflammation to prevent irreversible tissue damage.The article discusses the recent understanding of the pathogenesis of periodontitis, a chronic inflammatory disease affecting the supporting structures of teeth. Recent studies have revealed that the breakdown of host-microbe homeostasis can lead to dysbiosis and periodontitis in susceptible hosts. Keystone pathogens, such as *P. gingivalis*, and pathobionts, which are normally harmless commensals, exhibit synergistic interactions that enhance their colonization and persistence in an inflammatory environment, leading to tissue destruction and bone loss. The dysbiotic microbial communities thrive by exploiting tissue-destructive inflammation, creating a self-feeding cycle of escalating dysbiosis and inflammatory bone loss. The article highlights the role of host susceptibility, including immunodeficiencies, systemic diseases, and environmental factors, in the development of periodontitis. It also explores the cellular and molecular mechanisms involved in periodontal inflammation and bone loss, particularly the involvement of neutrophils, Th17 cells, and regulatory T cells. Finally, the article discusses therapeutic strategies targeting host signaling pathways to manage periodontitis, emphasizing the importance of inhibiting inflammation to prevent irreversible tissue damage.