With the availability of the complete DNA sequences of a wide range of organisms, structural biologists are faced with new opportunities and challenges in “structural genomics”. Research in structural genomics is focused on gene products with unknown structures, unknown functions, and minimal similarity to previously studied proteins. A precisely formulated initial goal of structural genomics was to investigate representatives of all protein families, and thus to cover a large part of the protein universe with three-dimensional structures. My research group is specialized in the use of nuclear magnetic resonance (NMR) spectroscopy for studies of proteins and represents this technique in the California-based Joint Center for Structural Genomics (JCSG: www.jcsg.org), which is one of four large-scale consortia in the NIH-funded Protein Structure Initiative (PSI: www.nigms.nih.gov/Initiatives/PSI/). When compared to structure determination by X-ray crystallography, which is the principal technique used by the JCSG, the NMR method is complementary by the fact that atomic resolution structures and other function-related data can be obtained under solution conditions close to the physiological milieu in body fluids. By generating data on protein structure, stability, dynamics and intermolecular interactions in solution, NMR thus has an exciting role in the longer-term challenge leading from the expanding protein structure universe to new insights into protein functions and chemical biology.