Viruses are obligate intracellular parasites that rely on the host cell for expansion.With the development of global analyses techniques like transcriptomics, proteomics andsiRNA library screening of complete cellular gene sets, a large range of host cell factorshave been discovered that either support or restrict virus growth. Here we summarize someof the recent findings and focus our discussion on the hepatitis C virus and the humanimmunodeficiency virus, two major pathogens that threat global health. The identificationof cellular proteins affecting multiple viruses points to the existence of centralregulation nodes that might be exploited for both, a quantitative description ofhost-virus interactions within single infected cells and the development of novel,broad-spectrum antiviral drugs.