Our work focuses on the development and application of technologies to comprehensively analyze the complement of small molecules in biological specimens, the metabolome. We have created a robust platform that uses a combination of liquid chromatography tandem mass spectrometry (LC-MS)-based methods to enable analyses of hundreds of compounds associated with cardiometabolic traits and diseases. Compounds measured by the platform broadly cover the metabolome and range from polar metabolites, such as lactate and organic acids, to nonpolar lipids. The methods also measure thousands of signals from yet to be identified metabolites and potentiate discovery of novel metabolites. Ongoing technology development efforts include creation of new analytical techniques and refinement of software tools to support metabolomics informatics workflows. Our research in diabetes and metabolic diseases is highly collaborative, with several ongoing studies of human cohorts that aim to identify early metabolic changes associated with risk of incident disease, including impact of the microbiome, diet and other potential modifiers such as lifestyle. Complementing the human cohort studies, the lab’s metabolomics capability is leveraged to dissect the roles of specific metabolites and pathways in biological models of diabetes and metabolism, including the use of stable isotope tracers. Our overall goal is to contribute to discovery of new markers of disease, factors that reduce disease risk, and avenues for therapeutic intervention.