Proteomics combined with bioinformatics has emerged as an important tool to extract detailed information of cellular signaling mechanisms [13] . With modern mass spectrometry (MS) -based approaches it is possible to identify and quantify thousands of proteins from cellular samples, as illustrated by Luber et al. who studied subset-specific viral recognition in dendritic cells [14] . Most of the large scale quantitative proteomics experiments, however, have focused on studying changes in protein abundances in whole cell lysates or individual organelles [14, 15] . The use of subcellular proteomics provides a deeper insight into cellular events as protein abundancies can be studied on the level of different subcellular compartments and also protein translocations between different cell parts can be detected [16, 17] . Moreover, pathway and network analyses can provide mechanistic insights by subsequently linking the proteins found to be differentially regulated to the underlying cellular functions and other key players known to be involved in these events. Here, we have used quantitative subcellular proteomics combined with bioinformatics to provide a global view of host-pathogen-interactions during influenza A virus infection of human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection.