Metabolomics is instrumental in the analysis of disease mechanisms and biomarkers of disease. The human metabolome is influenced by genetics and environmental interactions and reveals characteristic signatures of disease. Population studies with metabolomics require special study designs and care needs to be taken with pre-analytics. Gas chromatography coupled to mass spectrometry, liquid chromatography coupled to mass spectrometry or NMR are popular techniques used for metabolomic analyses in human cohorts. Metabolomics has been successfully used in the biomarker search for disease prediction and progression, for analyses of drug action and for the development of companion diagnostics. Several metabolites or metabolite classes identified by metabolomics have gained much attention in the field of diabetes research in the search for early disease detection, differentiation of progressor types and compliance with medication. This review summarises a presentation given at the ‘New approaches beyond genetics’ symposium at the 2015 annual meeting of the EASD.