In this context, the sequencing of

In this context, the sequencing of the human genome has moved systems biology into the forefront of biomarker discovery. However, the fields of genomics and proteomics have yet to deliver any biomarkers that are clinically applicable, and none have gone beyond the discovery phase (6). This lack of translation and validation could stall progress toward biomarker qualification in critical illnesses and hinder the usefulness of systems biology in the process. It has also brought about the realization that the sequencing of the human genome alone cannot provide the insight that is needed to unravel the complexity of disease, particularly acute, severe illnesses. This is a scientific challenge of the systems biology approach and highlights the need for new knowledge of the relationships and interactions between the components of the system (Figure 2). Monitoring fluctuations of certain metabolites (endogenous low–molecular weight molecules) in body fluids, such as blood (including plasma and serum) and urine, is an important way to detect various human pathologies, including cancer, cardiovascular disease, diabetes, and drug toxicity (6–15). These data are also needed to construct powerful top-down systems biology tools that link the “omics” disciplines (16). This top-down idea is based on the principle that small molecule metabolites are at the top of systems biology continuum and that metabolites reflect and magnify (several thousands of times) events that occur at the level of the genome, transcriptome, and proteome (Figure 2) (17, 18). Undoubtedly, metabolomics could have very meaningful applications in critical care medicine because acute illness most often causes significant disruption in biochemical homeostasis. Unfortunately, it is still in its infancy, which may be due, in part, to a lack of understanding of metabolomics science by clinical researchers. In the present article, we describe principles of metabolomics with a special emphasis on the existing challenges of its application to critical care medicine, including sample collection and handling, advantages and disadvantages of available analytical platforms, and data interpretation.