The Architecture et Fonction des Macromolécules Biologiques (AFMB) laboratory (http://www.afmb.univ-mrs.fr), a research centre in structural biology located on the campus of Luminy, Marseille, France, belongs to the Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU) and is affiliated to the federative structure “Infectiopôle, du Malade à la Molécule”. The AFMB lab was created well before the worldwide structural genomics initiatives aimed at documenting the structural proteome, but has rapidly made important contributions to this area through several French and European programs aimed at implementing a multidisciplinary approach to document the architectures of proteins and their functional implications. While protein crystallography was our pioneering activity and is still the main technique in use in the lab, electron microscopy has recently been developed as a complementary technique to address large molecular assemblies. Today, the AFMB lab gathers seven research teams and has developed a complete structural proteomics platform that brings together facilities for parallel and robotized cloning, expression, purification and crystallization through high-throughput approaches, and which is extensively used by internal and external users. Coupled to a chemical biology activity, a second platform has been developed for rapid screening of libraries of chemical compounds through automated activity assays for identification of potential antiviral drug candidates. The expertise and hardware required for specialized bioinformatics applied to databases dedicated to carbohydrate-active enzymes or viral enzymes and to structure computation are present as well.