Influenza viruses are accountable for annual epidemics worldwide that result in significant morbidity and mortality. In preschool and school-aged children, prospective surveillance of influenza demonstrates yearly infection rates of 15–42%. Children can easily transmit the virus to other children, to employees in day-care and school settings, and to family members. Two classes of antiviral drugs, the adamantine derivatives (amantadine, rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir), have been approved for treatment and prophylaxis of influenza in the pediatric population. Duration of clinical symptoms decreases and daily activities are resumed sooner when therapy is begun within 48 hours of the onset of influenza symptoms. Mechanism of action, adverse effects, and development of resistant variants differ between the two drug classes. To our knowledge, head-to-head clinical trials between the classes and involving the neuraminidase inhibitors are nonexistent. Antiviral agents do not replace the annual influenza vaccine, and clinical trials indicate that amantadine, rimantadine, zanamivir, and oseltamivir are safe and effective for administration in the pediatric population.