Advances in genomics and proteomics increasingly contribute to the understanding of signal transduction pathways that control growth, differentiation, and death of cells. Since defects in these processes may result in the expression of inherited and or acquired disease, the identification of candidate disease genes and modifier genes by parallel use of genotyping together with an integrated study of gene expression and metabolite levels is instrumental for future health care. This approach, called systems biology, aims to recognize early onset of disease, institute preventive treatment, and identify new molecular targets for novel drugs in cancer, cardiovascular and metabolomic disease (e.g., diabetes), and neurodegenerative disorders. Gene interaction networks have recently been demonstrated, in which hub genes, that is, genes that show the highest level of interactions with other genes, play a special role. Hub genes, often chromatin regulators, may act as modifier genes (genes that modify the effect of other genes) in multiple mechanistically unrelated genetic diseases in humans. In addition, it has been shown that small metabolites such as hormones and cytokines, or proteins/enzymes such as C reactive protein (C-RP) and matrix metaloproteinase (MMP), reflect disease status in case of oral cancer, asthma, or periodontal and cardiac disease. Many of these molecular targets, as well as pathogen-specific DNA and RNA sequences, can be measured in oral fluids, providing a unique opportunity to develop novel noninvasive diagnostic tests. Efforts so far concentrate on the use of lab-on-a-chip technology in combination with novel reporters and microsensor arrays to measure multianalytes in oral fluids. Handheld devices that perform sensitive detection of multiple analytes in oral fluid will be obtainable in the near future.