The Human Metabolome Database (HMDB) has been updated to version 4.0, representing the most significant upgrade in its history. This update includes a nearly threefold increase in the number of fully annotated metabolites, a nearly fourfold increase in experimental spectra, and a nearly 60-fold increase in illustrated metabolic pathways. New features include predicted MS/MS and GC-MS reference spectral data, predicted metabolite structures, and data on metabolite-SNP interactions and drug effects on metabolite levels. The database has also improved its chemical taxonomy, spectral viewing, and searching tools, enhancing its usability and applicability in various fields such as nutrition, biochemistry, clinical chemistry, and metabolomics.The Human Metabolome Database (HMDB) has been updated to version 4.0, representing the most significant upgrade in its history. This update includes a nearly threefold increase in the number of fully annotated metabolites, a nearly fourfold increase in experimental spectra, and a nearly 60-fold increase in illustrated metabolic pathways. New features include predicted MS/MS and GC-MS reference spectral data, predicted metabolite structures, and data on metabolite-SNP interactions and drug effects on metabolite levels. The database has also improved its chemical taxonomy, spectral viewing, and searching tools, enhancing its usability and applicability in various fields such as nutrition, biochemistry, clinical chemistry, and metabolomics.