Over the past few years a novel class of antiviral agents, the neuraminidase inhibitors, has been found to be safe and effective in the prevention and treatment of influenza. Previously available agents, the M2 inhibitors amantadine and rimantadine, could only be used to treat influenza A infections and resistance develops rapidly. Zanamivir (Relenza) and oseltamivir (Tamiflu), the two clinically available neuraminidase inhibitors, are effective for treating both influenza A and B infections in adults and children and have also been shown to reduce the frequency of antibiotic-requiring complications of influenza infections. Inhaled zanamivir has shown benefit in treating acute influenza with mild to moderate underlying asthma or chronic obstructive pulmonary disease. Studies are needed to examine the use of these agents, alone or in combination with M2 inhibitors or ribavirin, in the management of severe infections in hospitalized patients and immunocompromised hosts. Studies are also needed to address other groups at increased risk for influenza complications, such as pregnant women and children below one year of age.