Abstract: Human oral cavity is colonized by various microbial communities which play an important role in the initiation and progression of periodontitis. However, it is still not clear how these microbial communities mediate the disease. With the rise of metagenomics research, polymicrobial synergy and dysbiosis (PSD) model, a new periodontitis pathogenesis mechanism, was proposed. The importance of the microbial communities acting as a whole system in the development of periodontitis is gradually recognized. Host susceptibility, as another key factor in the initiation of the disease, is vital in PSD model. This article reviews the mechanisms of the PSD model and its research progress in periodontitis as well as some other diseases and briefly highlights the positive significance in terms of prevention and treatment of periodontitis in order to provide insights and perspectives for the future periodontal researches.