The development of the neuraminidase inhibitors has revolutionized the management options for influenza. Zanamivir was the first such inhibitor to be approved for the treatment of influenza in humans. It is delivered by inhalation to the respiratory tract, which is the site of viral replication, in order to ensure immediate antiviral activity. Early treatment with zanamivir in clinical trials rapidly reduced the severity and duration of influenza symptoms and associated complications. Furthermore, chemoprophylaxis with zanamivir was shown to be effective in the prevention of influenza illness. To date, there is no evidence for the emergence of clinically significant zanamivir–resistant isolates. In conclusion, zanamivir offers a useful complementary strategy to vaccination in the effective management of influenza.