Lipid rafts are sphingolipid- and cholesterol-enriched membrane microdomains, which are involved in entry, assembly and budding of various types of viruses. Identification of rafts associated proteins modified by virus infection could therefore provide novel insights into the mechanisms of virus infection as well as the development of new biomarkers for diagnosis and drug development. Proteomic approaches, such as LC-ESI-MS/MS, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), two-dimensional difference gel electrophoresis (2D-DIGE), isotope-coded affinity tags (ICAT), Proteolytic ¹⁸O Labeling, isotope Tags for Relative and Absolute Quantification (iTRAQ), Stable Isotope Labeling with Amino acids in Cell culture (SILAC) and Multidimensional Protein Identification Technology (MudPIT), provide the large scale and unbiased platform to determine the dynamic profiles of the lipid rafts proteome. In this review, we summarized the research advance regarding modern proteomics analysis of host lipid rafts alterations in response to diverse virus infection.