Periodontium that anchors the teeth to the jaws comprises of gingiva, periodontal ligament, cementum, and alveolar bone. At clinically healthy sites, the balance between the microbiota and periodontium is beneficial, resulting in resistance to colonization by commensal periopathogens and also triggering well-defined responses of the host innate immune system. By contrast, at diseased sites there is an alteration of defense mechanisms in the periodontium resulting from heterogeneous etiologies including complex biofilm in the sub gingival microenvironment, which is influenced and modulated by the host's immune and inflammatory responses. The present review will focus on the cells of adaptive immune response like B- and T-cells in periodontal disease progression.