ZINC is a free public resource for ligand discovery, containing over 20 million commercially available molecules in biologically relevant representations. The database is maintained and curated to ensure a high purchasing success rate and is freely available at zinc.docking.org. ZINC has grown 10-fold in size since its inception, with improved 3D molecular representations and new features. It supports various chemoinformatic techniques and is designed to be useful for research by being large, purchasable, relevant, and in biologically applicable forms. The database includes compounds from over 100 vendors and annotated compounds from over 20 databases. ZINC offers subsets for easy creation, editing, sharing, docking, downloading, and conveyance to vendors for purchase. The user interface has been rewritten to facilitate new queries and provide flexibility and power for both beginners and experts. ZINC now supports pH-dependent representations, improved functional group filtering, and improved user interface features such as text queries, authentication, and shopping carts. Examples demonstrate how ZINC can be used to acquire libraries for docking screens, find purchasable analogs, identify specialist vendors, generate decoys for docking, prioritize hits for purchase, and answer other challenging questions.ZINC is a free public resource for ligand discovery, containing over 20 million commercially available molecules in biologically relevant representations. The database is maintained and curated to ensure a high purchasing success rate and is freely available at zinc.docking.org. ZINC has grown 10-fold in size since its inception, with improved 3D molecular representations and new features. It supports various chemoinformatic techniques and is designed to be useful for research by being large, purchasable, relevant, and in biologically applicable forms. The database includes compounds from over 100 vendors and annotated compounds from over 20 databases. ZINC offers subsets for easy creation, editing, sharing, docking, downloading, and conveyance to vendors for purchase. The user interface has been rewritten to facilitate new queries and provide flexibility and power for both beginners and experts. ZINC now supports pH-dependent representations, improved functional group filtering, and improved user interface features such as text queries, authentication, and shopping carts. Examples demonstrate how ZINC can be used to acquire libraries for docking screens, find purchasable analogs, identify specialist vendors, generate decoys for docking, prioritize hits for purchase, and answer other challenging questions.