This article provides an overview of periodontal disease diagnosis that uses clinical parameters and biomarkers of the disease process.This article discusses the use of biomarkers of disease that can be identified at the tissue, cellular, and molecular levels and that are measurable in oral fluids such as saliva and gingival crevicular fluid. Biomarkers identified from these biologic fluids include microbial, host response, and connective tissue-related molecules that can target specific pathways of local alveolar bone resorption. Future prospects for oral fluid-based diagnostics that use micro-array and microfluidic technologies are presented.