In the field of oral disease diagnosis, there has been a steady growing trend during the last 2 decades to develop tools to monitor periodontitis. From physical measurements such as periodontal probing to sophisticated genetic susceptibility analysis and molecular assays for the detection of biomarkers on the different stages of the disease, substantial improvements have been made on the understanding of the mediators implicated on the initiation and progression of periodontitis. At the same time, this evolutionary process has promoted the discovery of new biomarkers and the development of new therapeutic approaches mainly using host modulation. Moreover, new diagnostic technologies such as nucleic acid and protein microarrays and microfluidics are under development for risk and comprehensive screening of biomarkers. These recent advances are leading to the development of more powerful diagnostic tools for practitioners to optimize their treatment predictability. It is clear that no single marker will fulfill all the criteria necessary for assessment of the clinical state of the periodontium, and future research should be directed at the production of "marker packages".