Frontiers of high-throughput metabolomics

•Metabolomics enables rapid measurements at 10–100 times higher throughput than proteomics.•The achievable throughput opens entirely new scientific and medical opportunities.•Key limitations are study design and data analyses to generate testable molecular hypotheses. Large scale metabolomics studies are increasingly used to investigate genetically different individuals and time-dependent responses to environmental stimuli. New mass spectrometric approaches with at least an order of magnitude more rapid analysis of small molecules within the cell's metabolome are now paving the way towards true high-throughput metabolomics, opening new opportunities in systems biology, functional genomics, drug discovery, and personalized medicine. Here we discuss the impact and advantages of the progress made in profiling large cohorts and dynamic systems with high temporal resolution and automated sampling. In both areas, high-throughput metabolomics is gaining traction because it can generate hypotheses on molecular mechanisms and metabolic regulation. We conclude with the current status of the less mature single cell analyses where high-throughput analytics will be indispensable to resolve metabolic heterogeneity in populations and compartmentalization of metabolites.