The aim of this chapter is to focus on the pathogenesis of periodontal diseases. Gingivitis and periodontitis are caused by bacteria that colonize the gingival crevice and attach to the tooth surface. The pathogenic potential of the bacteria within the plaque varies from gingiva, site to site. Small amounts of plaque can be tolerated without causing periodontal disease, may be because of the host defense. This chapter covers the junctional epithelium, role of bacterial invasion, role of exotoxins, role of cell constituents, role of enzymes, host derived bone-resorbing agents, and role of cytokines. Junctional epithelium is the tissue most directly challenged by the pathogenic plaque bacteria. The microbial mass releases large quantities of metabolites like butyric acid and propionic acids, which are toxic to periodontal tissues.