The connection between oral health and systemic disease has led to new strategies to detect disease, with the major advantage of easy access to oral cavity structures and fluids. The mouth can also provide evolutionary insights into dietary habits of past societies and give clues to disease states that early peoples encountered. These insights are important for providing context for understanding the present condition of oral and general health globally. This session will present five topics with a universal theme and emphasis on bioinformatics for a timely description of new approaches involving genomics in relation to disease and overall health. An anthropological overview of global impact of dental caries and its historical relationship to systemic health will be followed by a discussion of the biology of risk for caries through analysis of the oral microbiome. The salivary diagnostics dictionary can lead to detection of early carcinoma and comparison of salivary gene expression patterns in healthy and diseased individuals using proteome and transcriptome databases. Anti-resorptive treatment for osteoporosis and, at higher doses, for cancer therapy is associated with osteonecrosis of the jaw (ONJ); causes, prevalence, and potential treatments of ONJ will be discussed. Finally, the link between inflammation and protease-substrate interactions during periodontal disease will be evaluated through the new field of degradomics.