Viruses hijack host metabolism to complete their life cycle. Here, Wobus and colleagues show that host cell metabolism is also important for modulating replication of murine norovirus (MNV). Using metabolomics profiling they found that infection of mouse macrophages by MNV increases host cell metabolism. To establish the effects of this increase in host metabolic activity they inhibited glycolysis, which attenuated MNV infection. By contrast, although the pentose phosphate pathway and oxidative phosphorylation were also increased during infection, those pathways only have a minor effect on MNV infection. The authors went on to show that glycolysis is important during the early steps in the viral life cycle following viral entry and capsid uncoating. Finally, they report that MNV infection activated the protein kinase Akt, which is a master regulator of cellular metabolism.