For generations, blood has been the medium of choice for diagnosing most diseases and conditions. The reason for this is mainly the limitations of technology. The concept of oral diagnostics is preferred to more invasive methods. In recent years, it has become evident that the salivary constituents become detectably altered in response to certain disease states. Even so, what is most impressive is that salivary biomarkers not only arise in correlation with oral disorders but also those of distal tissues and organs. This suggests that oral fluids may represent a substantial reservoir of molecular and microbial information capable of communicating the onset or presence of disease throughout the body. An initiative of the National Institute of Dental and Craniofacial Research created a roadmap to achieve these goals whereby, with the use of oral fluids as the diagnostic medium, it would become possible to scrutinize the health and/or disease status of patients. The real promise of salivary analysis use is the ability of the patient or clinician to directly and continuously assess disease status, progression and therapeutic efficacy. The sensitive analysis may even allow presymptomatic diagnosis. There are five major diagnostic alphabets available in saliva namely, proteins, messenger RNAs, micro-RNAs (mi-RNAs), metabolic compounds and microbes which offer substantial advantages for salivary diagnostics because, the state of the disease may be associated with detectable changes in one, but not all, dimensions. Recently, the Salivaomics Knowledge Base (SKB) has been established by aligning the salivary biomarker discovery. The SKB constitutes data repository, management system and web resource fabricated to support human salivary proteomics, transcriptomics, miRNA, metabolomics and microbiome research.