Periodontal diseases are characterized by a complex set of biologic interactions between a diverse and dynamic microbial ecosystem and the host’s multifaceted immune and inflammatory machinery. Such interactions between microbial pathogens and various host response systems play a critical role in the development and progression of periodontal disease via the release of inflammatory and immune mediators. Advances in periodontal disease diagnostic are moving toward methods whereby periodontal risk can be identified and quantified by detecting such inflammatory mediators in its sequential pathophysiology. Evidence suggests that acute-phase proteins acts as a non-redundant component of the humoral arm of innate immunity, as well as a tuner of inflammation. In Periodontal diagnostics, it has been a great challenge to determine biomarkers for screening and predicting the early onset of disease (prognostic tests) or evaluating the disease activity and the efficacy of therapy. Hence the need of advanced markers to accurately identify the disease with high sensitivity and specificity were sought. Acute phase proteins in general come close to fulfill these criteria.