Influenza viruses, similarly to other viruses, rapidly acquire de novo mutations when they replicate within their host cells.However, how the emergence of viral variants in the host is reflected at a global scale is still poorly understood. In a new study, Xue et al. used a deep-sequencing approach to analyse longitudinal samples from immunocompromised patients who had long-term influenza infections. The authors found that the same set of mutations had emerged independently in several patients, most commonly in the genes that encode haemagglutinin (HA) and neuraminidase. Furthermore, many of the mutations in HA had also reached high global frequency in the decade following patient infections. This study shows that viral evolution and variation in the host parallel evolution at a global scale. Understanding these dynamics will help to predict the evolution of influenza viruses and the design of more effective vaccines.