Influenza A and B viruses are considerable public health threats. Annual seasonal epidemics are driven by antigenic drift and cause an estimated 3–5 million severe cases and 290,000–650,000 deaths annually. The clinical presentation of seasonal influenza is typically an abrupt, uncomplicated acute respiratory illness with full recovery; however, it can lead to severe, life-threatening complications in individuals at high risk. Antigenic shift caused by reassortment of a seasonal influenza A virus with avian and/or swine influenza A viruses has led to unpredictable pandemics. The successful cross-species transmission of influenza A viruses requires key viral adaptations, including changes in receptor specificity and compatibility with host factors such as ANP32A. Host defence involves a layered innate response, which is antagonized by proteins, such as non-structural protein 1, and a robust adaptive immunity comprising cytotoxic CD8+ T cells targeting conserved internal proteins and B cells producing neutralizing antibodies. Diagnosis primarily depends on highly sensitive PCR-based methods and multiplexed rapid antigen tests. Prevention involves annually updated seasonal vaccines (including inactivated, live attenuated and protein-based vaccines), while treatment relies on early use of neuraminidase and polymerase acidic protein inhibitors. Research priorities include the development of improved vaccines and a better understanding of influenza virus transmission from animals to humans.