Hemagglutinin (HA) and neuraminidase (NA) are the two major surface proteins of influenza A virus (IAV). Initial attachment of the virus to the host cell is mediated by the binding of terminal sialic acids (Sia) of glycoconjugates to HA. At the final step of the infectious cycle NA cleaves Sia to ensure virus release from the cell surface. In this overview focus will be given to the structural details of Sia receptor binding and Sia cleavage and how this information in the case of NA has enabled the development of potent sialomimetic drugs by structure-based drug design.