Influenza viruses are highly transmissible, both within and between host species. The severity of the disease they cause is highly variable, from the mild and inapparent through to the devastating and fatal. The unpredictability of epidemic and pandemic outbreaks is accompanied but the predictability of seasonal disease in wide areas of the Globe, providing an inexorable toll on human health and survival. Although there have been great improvements in understanding influenza viruses and the disease that they cause, our knowledge of the effects they have on the host and the ways that the host immune system responds continues to develop. This review highlights the importance of the mucosa in defence against infection and in understanding the pathogenesis of disease. Although vaccines have been available for many decades, they remain suboptimal in needing constant redesign and in only providing short-term protection. There are real prospects for improvement in treatment and prevention of influenza soon, based on deeper knowledge of how the virus transmits, replicates and triggers immune defences at the mucosal surface.