Host cell attachment by influenza A viruses is mediated by the hemagglutinin glycoprotein (HA), and the recognition of specific types of sialic acid -containing glycan receptors constitutes one of the major determinants of viral host range and transmission properties. Structural studies have elucidated some of the viral determinants involved in receptor recognition of avian-like and human-like receptors for various subtypes of influenza A viruses, and these provide clues relating to the mechanisms by which viruses evolve to adapt to human hosts. We discuss structural aspects of receptor binding by influenza HA, as well as the biological implications of functional interplay involving HA binding, NA sialidase functions, the effects of antigenic drift, and the inhibitory properties of natural glycans present on mucosal surfaces.