Antiviral drugs are important in the management of seasonal influenza and critical to pandemic planning. Although several other classes of anti-influenza compounds exist, the neuraminidase (NA) inhibitors are currently the only option in most clinical settings. These drugs, zanamivir and oseltamivir, prevent the release of newly replicated influenza virions from infected cells. They are highly effective when used for treatment of seasonal influenza early in the course of infection, or for prevention when given soon after exposure. Treatment strategies for avian influenza infections in humans are still provisional owing to inadequate clinical data. As predicted by molecular studies, resistance to the NA inhibitors is now emerging, although at a level less significant than adamantane resistance. NA inhibitor resistance is a cause for concern if indeed some mutant strains of avian influenza are transmissible and pathogenic. In the near term, appropriate use of the available NA inhibitors will be of major benefit in lessening morbidity and mortality due to influenza infection. Priorities include developing appropriate formulations and guidelines for use of these drugs in children and people infected with avian influenza, study of the mechanisms and clinical significance of drug resistance, and identification of new antiviral therapies that target different points in the viral life cycle in order to limit the effect of emerging drug resistance.