Influenza virus remains a major public heath concern, both in its annual toll in death and debilitation and its potential to cause devastating pandemics. A number of recent surprising discoveries emphasize how little we know about influenza virus and its interaction with its hosts. These include the description of a novel viral protein encoded by an overlapping reading frame, the demonstration that the most abundant viral non-structural protein interferes with the induction of interferons by infected cells, and the finding that natural killer cells express activating receptors that detect viral cell-surface proteins. The introduction of improved methods for genetically manipulating influenza virus promises to revolutionize our understanding of viral replication and its interaction with the host innate and acquired immune systems, and will also enable the improvement of vaccines. Using knowledge of viral sequences recovered from archived or interred tissues from victims of the 1918 influenza pandemic, it is now possible to investigate why this virus was so pathogenic - it killed more than 20 000 000 people, most of whom were young adults in the prime of their lives.