We shall describe the historic evolution of influenza and the main pandemics of the 20th century. We shall talk about the structure of the influenza virus and of its antigenic variations, which bring about minor or major mutations, with the consequent persistence of the annual risk of epidemics and of potential pandemics. We shall analyse prevention, which is essentially based on the administra-tion of a safe and effective vaccine, made up of the strains (2 from virus A and one from virus B) recommended each year by a group of experts from the WHO. The risk of the next pandemic may decrease if we follow the WHO recommendations, which can be summarised as: adequate virus and epidemic surveillance and development of countrywide and worldwide prevention strategies.