Despite advances in therapeutics and biomedical research in oral health diseases that have transformed since the turn of this century and deepened our understanding of hallmarks of malady, resulting in the discovery and development of targeted therapies, the success rates of oral health disease diagnosis remains low. Opportunities have increased with the understanding of molecular basis of the periodontal diseases translating to the discovery, development and availability of targeted therapies that have brought meaningful benefit to patients with diverse infirmity. The encouraging results from neoadjuvant therapies for patients with severe periodontal diseases, call for the identification of new accu¬rate predictors so that the appropriate therapy can be tailored better for individual patients. The overall aim of this review was the emphasis on the molecular mechanism of diagnosis and prognosis in an attempt to identify and predict the response of periodontal disease to further treatment modality.