Healthy children are high transmitters of influenza and can experience poor influenza outcomes. Many questions remain about the efficacy and impect of preventive measures because most existing studies report imprecise proxies of influenza incidence, do not follow subjects throughout the entire influenza season and across multiple influenza seasons, or do not control for important factors such as timing of implementation and social contact patterns. Modeling and simulation are key methodologies to answer questions regarding influenza prevention. While vaccination may be the most efficacious existing intervention, variations in circulating strains and children's immune systems keep current vaccines from being fully protective, necessitating further clinical and economic studies and technology improvements. Hand hygiene appears to be an important adjunct but improving compliance, standardizing regimens and quantifying its impact remain challenging. Future studies should help better define the specific indications and circumstances for antiviral use and the role of nutritional supplements and nonpharmaceutical interventions.