The illness attack rate and annual morbidity caused by infection with influenza is high in schoolchildren. Because schoolchildren are 1 of the most important sources of community-wide transmission of influenza, vaccinating them could have a major effect on reducing morbidity and mortality in older adults. Stochastic modeling shows that a vaccination rate as low as 20% in schoolchildren reduces overall mortality in adults aged ≥64 years more effectively than a vaccination rate of 90% for older adults. Additional modeling shows that vaccinating schoolchildren against influenza is optimal for reducing morbidity and mortality caused by influenza in the overall population. Although supported by simulated models, the benefits of mass vaccination need to be confirmed in a real-world setting. The best way to demonstrate the effectiveness of mass vaccination of schoolchildren is to implement the process in several localities in several states by using properly designed studies that incorporate accurate viral surveillance with at least 10 pairs of intervention and comparison populations.