IUPHAR-DB (www.iuphar-db.org) is an open access database providing detailed, expert-driven annotation of the pharmacology of drug target systems from peer-reviewed primary literature sources. The database is maintained by a team of skilled curators, with guidance from the IUPHAR Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) and an international network of ~700 expert contributors. Here, we present several recent developments that significantly increase the scope and enhance the utility of IUPHAR-DB. The coverage of targets in IUPHAR-DB currently stands at 627 genes encoding G protein-coupled receptors, voltage- and ligand-gated ion channels, nuclear hormone receptors and the 10 enzymes of the lanosterol biosynthesis pathway. A joint initiative between NC-IUPHAR and the British Pharmacological Society (BPS) has led to the recent launch of a new open access portal, www.guidetopharmacology.org, which integrates IUPHAR-DB and the BPS Guide to Receptors and Channels (GRAC) and currently documents quantitative pharmacological information on over half of the targets of current licensed drugs. The database now contains over 3800 distinct ligand molecules, ranging from synthetic organic chemicals to natural products and peptides; an important recent addition is the curation of the sequences and post-translational modifications of ~500 endogenous peptide ligands. Information provided about ligands includes 2D structures, calculated physical-chemical properties, synonyms, selectivity data at targets and links to external chemical structure databases and to co-crystallised 3D structures in the Protein Data Bank. The database search interface has also been enhanced, allowing for navigation of the ligand chemical structure space covered by IUPHAR-DB and GRAC through text, identity, similarity, substructure and SMARTS-pattern queries. As an established internationally-recognised resource for pharmacologists, these recent developments to IUPHAR-DB further extend its usability, facilitate exploratory research in pharmacology and drug discovery, educate the next generation of biomedical and clinical scientists, and provide the general public with accurate information on how drugs work.