To monitor health status, disease onset and progression, and treatment outcome non-invasively is a most desirable goal in the health care delivery and health research. There are three prerequisites necessary to reach this goal: 1. A non-invasive method for collecting biological samples. 2. Specific biomarkers associated with health or disease. 3. A technology platform to rapidly discriminate the biomarkers. An initiative catalysed by the National Institute of Dental and Craniofacial Research (NIDCR) has created a roadmap to achieve this goal through the use of oral fluids as the diagnostic medium to scrutinize the health and disease status. This is an ideal opportunity to bridge state-of-the-art saliva-based biosensors and disease-discriminatory salivary biomarkers in diagnostic applications. Oral fluid, often called the mirror of the body, is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous. This review presents the translational value of saliva as a credible clinical diagnostic fluid and the scientific rationale for such use.