The 2025 Nucleic Acids Research database issue contains 185 papers spanning biology and related areas. Seventy three new databases are covered, while resources previously described in the issue account for 101 update articles. Databases most recently published elsewhere account for a further 11 papers. Nucleic acid databases include EXPRESSO for multi-omics of 3D genome structure (this issue's chosen Breakthrough Resource and Article) and NAIRDB for Fourier transform infrared data. New protein databases include structure predictions for human isoforms at ASpdb and for viral proteins at BFVD. UniProt, Pfam and InterPro have all provided updates: metabolism and signalling are covered by new descriptions of STRING, KEGG and CAZy, while updated microbe-oriented databases include Enterobase, VFDB and PHI-base. Biomedical research is supported, among others, by ClinVar, PubChem and DrugMAP. Genomics-related resources include Ensembl, UCSC Genome Browser and dbSNP. New plant databases cover the Solanaceae (SolR) and Asteraceae (AMIR) families while an update from NCBI Taxonomy also features. The Database Issue is freely available on the Nucleic Acids Research website (https://academic.oup.com/nar). At the NAR online Molecular Biology Database Collection (http://www.oxfordjournals.org/nar/database/c/), 932 entries have been reviewed in the last year, 74 new resources added and 226 discontinued URLs eliminated bringing the current total to 2236 databases.