The avian influenza virus needs to mutate to cross the species barrier and to infect and replicate within mammalian cells. Scientists have now deciphered the structure of the avian influenza virus’s polymerase when it interacts with a human protein essential for the virus to replicate within the cell. The structure of this replication complex provides important information about the mutations that avian influenza polymerase must undergo to adapt to mammals, including humans. These results can help scientists monitor the evolution and adaptability of bird flu strains, such as H5N1 or H7N9, towards infecting other species.