Protein-protein interactions are fundamental to all biological processes, and a comprehensive determination of all protein-protein interactions that can take place in an organism provides a framework for understanding biology as an integrated system. The availability of genome-scale sets of cloned open reading frames has facilitated systematic efforts at creating proteome-scale data sets of protein-protein interactions, which are represented as complex networks or 'interactome' maps. Protein-protein interaction mapping projects that follow stringent criteria, coupled with experimental validation in orthogonal systems, provide high-confidence data sets immanently useful for interrogating developmental and disease mechanisms at a system level as well as elucidating individual protein function and interactome network topology. Although far from complete, currently available maps provide insight into how biochemical properties of proteins and protein complexes are integrated into biological systems. Such maps are also a useful resource to predict the function(s) of thousands of genes.