Infectious diseases comprise some of the leading causes of death and disability worldwide. Interactions between pathogen and host proteins underlie the process of infection. Improved understanding of pathogen-host molecular interactions will increase our knowledge of the mechanisms involved in infection, and allow novel therapeutic solutions to be devised. Complete genome sequences for a number of pathogenic microorganisms, as well as the human host, has led to the revelation of their protein-protein interaction (PPI) networks. In this post-genomic era, pathogen-host interactions (PHIs) operating during infection can also be mapped. Detailed systematic analyses of PPI and PHI data together are required for a complete understanding of pathogenesis of infections. Here we review the striking results recently obtained during the construction and investigation of these networks. Emphasis is placed on studies producing large-scale interaction data by high-throughput experimental techniques.