The Molecular Libraries Small Molecule Repository (MLSMR) is a component of the National Institutes of Health (NIH) Roadmap Molecular Libraries initiative for the creation of an NIH small molecule library and screening centers. The Small Molecule Repository will offer public sector biomedical researchers access to small organic molecules that can be used as chemical probes to study cellular pathways in greater depth and will provide new ways to explore the functions of major components of the cell in health and disease. In order to provide these benefits, the library of small molecules must contain a sufficient number of diverse compounds to be screened for a large number of possible new activities and applications. To build such a library, the MLSMR will be established to acquire, maintain, and distribute a collection of up to 500,000 chemically diverse small molecules of both known and unknown activities from government, academic, industry and commercial sources. Over time, this collection will be expanded and modified to include compounds that are capable of interacting with an increasing number and diversity of biomolecular target domains. The development of such libraries will provide probes for studying molecular events, pathways, and networks in biologic systems that span the scale from single cells to whole organisms. The MLSMR will acquire the compounds, conduct quality control analyses, and store them in manner that allows easy access and tracking and maintains the compounds under optimal conditions. The MLSMR will distribute these compounds in plated sets to the Molecular Libraries network of high-throughput screening centers for biological evaluation.