Metabolomics, the global interrogation of the biochemical components in a biological sample, has become an important complement to genomics and proteomics to aid in the understanding of pathophysiology. Major advantages of metabolomics are the size of the metabolome relative to the genome or proteome and the fact that it provides a view of the existing biochemical phenotype. As such, metabolomics is fast becoming an important discovery tool for new diagnostic and prognostic biomarkers. Although many methods exist for performing metabolomics, relatively few have led to successful development of new diagnostic tests. This review will aid the reader in understanding various metabolomic methods and their applications, as well as some of their inherent advantages and disadvantages. In addition, we present one example of the application of metabolomics to the identification of new fasting blood biomarkers for the diagnosis and monitoring of insulin resistance.