New Pathways to Discovery. This theme addresses the need to understand complex biological systems. Future progress in medicine will require quantitative knowledge about the many interconnected networks of molecules that comprise cells and tissues, along with improved insights into how these networks are regulated and interact with each other. New Pathways to Discovery also sets out to build a better “toolbox” for today’s biomedical researchers. To fully capitalize on the recent sequencing of the human genome and many new discoveries in molecular and cell biology, the research community needs wide access to technologies, databases, and other scientific resources that are more sensitive, more robust, and more easily adaptable to researchers’ individual needs. Roadmap initiatives within this theme address technologies and approaches necessary to meet contemporary research challenges, including building blocks and pathways, molecular imaging, the development of small-molecule libraries, bioinformatics and computational biology, nanomedicine, and structural biology. We will issue new Requests for Applications (RFAs) in FY 2004 for National Technology Centers for Networks and Pathways, National Centers for Biomedical Computing, Centers for Innovation in Membrane Protein Production, as well as investigator-initiated grants for related research in structural biology, metabolomics technology development, and proteomics. In addition, we will support development of new screening centers for bioactive small molecules, a publicly accessible cheminformatics reference database to be housed at NIH’s National Center for Biotechnology Information, and a database and core facility dedicated to synthesizing and distributing molecular imaging probes. The agency will also begin planning a series of nanomedicine centers that will be launched in 2005. These centers will focus on quantitative measurement of biological processes at the nanoscale and the engineering of new tools to intervene at the nanoscale or molecular level. This research will help scientists construct synthetic biological devices, such as miniature, implantable pumps for drug delivery or tiny sensors to scan for the presence of infectious agents or metabolic imbalances.