Oseltamivir is a neuraminidase inhibitor approved for treatment and prevention of influenza virus infection. Oseltamivir resistance caused by a single amino acid substitution from histidine (H) to tyrosine (Y) at position 274 of the neuraminidase active site has been reported in persons infected both experimentally and naturally with influenza A virus subtype H5N1. Evidence suggests that using lower doses of oseltamivir or shorter-than-recommended treatment periods can contribute to emergence of viral resistance. Currently, oseltamivir is being used in several countries that may be affected by epidemics of H5N1. Therefore, monitoring for oseltamivir-resistant strains of H5N1 during oseltamivir administration is essential for outbreak management and prevention.