In healthy individuals, influenza causes self-limited disease. An appropriate immune response leads to a rapid viral clearance, thereby limiting the duration of viral shedding to <10 days in most adults. In contrast, subjects with an impaired immune response might not efficiently clear influenza infection, thereby leading to additional replication cycles and higher viral loads. In these circumstances, given the intrinsic abilities of this RNA virus to accumulate point mutations, the likelihood of the emergence of new quasi species increases rapidly. According to the resulting phenotypic changes, new emerging mutants can escape the different environmental constraints (antigenic drift), including the host's immune responses and drug pressures. At an individual level, such adapted viruses may contribute to viral persistence and decrease the efficacy of antiviral drugs. On a wider level, new drifted strains lead to vaccine escape and could promote progressive adaptation of animal strains to humans. In this issue, Baz et al. [1] describe a stem cell transplant recipient presenting with a chronic influenza infection for