Recently, some 50 biologists and officials from government funding agencies met at the NIH campus in Bethesda, MD to explore the interdisciplinary science and organization of the emerging field of structural proteomics. Structural proteomics aims to discover most macromolecular complexes and characterize their three-dimensional structures and functional mechanisms in space and time. The goal seems daunting, but the consensus was that the prize would be commensurate with the effort invested, given the importance of molecular machines and functional networks in biology and medicine. Identification of assemblies and transient complexes combined with their structural and functional characterization will allow us to understand, control, design, and change the functioning of larger biological systems as well as to contribute to drug target discovery, lead discovery, and lead optimization for treatment of human disease.