Metabolomics, which is defined as the comprehensive analysis of metabolites in a biological specimen, is an emerging technology that holds promise to inform the practice of precision medicine. Historically, small numbers of metabolites have been used to diagnose complex metabolic diseases as well as monogenic disorders such as inborn errors of metabolism. Current metabolomic technologies go well beyond the scope of standard clinical chemistry techniques and are capable of precise analyses of hundreds to thousands of metabolites. Consequently, metabolomics affords detailed characterization of metabolic phenotypes and can enable precision medicine at a number of levels, including the characterization of metabolic derangements that underlie disease, discovery of new therapeutic targets, and discovery of biomarkers that may be used to either diagnose disease or monitor activity of therapeutics.The goal of precision medicine is to design disease prevention and clinical care strategies taking into account individual variability in environment, lifestyle, genetics, and molecular phenotype. The application of clinical genomics in cancer to inform selection of therapies and predict outcomes has been the vanguard of the field. Using a microscope as an analogy, genomic tools constitute a powerfully informative objective lens through which to examine individual variability, but it does not provide a view to other biomolecules, such as metabolites, which also define molecular phenotypes. Ideally, a molecular microscope for precision medicine would be equipped with additional objectives to examine biochemistry more broadly. There are decades of precedence for using analyses of small numbers of metabolites to diagnose disease and impact clinical care—for example, the development of blood glucose test strips in the 1950s to test for diabetes () or measuring phenylalanine in newborns to screen for phenylketonuria ). Indeed, measurable changes in metabolite levels occur in response to both complex disease and monogenic disorders, and in contrast to the genome, these changes can exhibit tissue specificity and temporal dynamics. Metabolomics is an emerging field and is broadly defined as the comprehensive measurement of all metabolites and low-molecular-weight molecules in a biological specimen. Because metabolomics affords profiling of much larger numbers of metabolites than are presently covered in standard clinical laboratory techniques, and hence comprehensive coverage of biological processes and metabolic pathways, it holds promise to serve as an essential objective lens in the molecular microscope for precision medicine.