Influenza is a disease that deeply affects millions of people every year. There has not been any drug effective against all strains. Neuraminidase (NA) is the major surface glycoprotein of the influenza virus, which possesses critical enzymatic activity and has been considered as a suitable target for designing agents against influenza viruses. Here we review the structure and functions of this enzyme and touch upon the structure-activity relationship (SAR) of existing influenza neuraminidase inhibitors (NAIs).