In areas endemic for schistosomiasis having limited healthcare, targeted drug treatment of school-age children is recommended for control of Schistosoma -associated morbidity. However, optimal timing, number, and frequency of treatments are not established. Because longitudinal studies of long-term impact of treatment are few, for current policy considerations we performed quantitative simulation (based on calibrated modeling of Schistosoma-associated disease formation) to project the impact of different school-age treatment regimens. Using published efficacy data from targeted programs, combined with age-specific risk for growth retardation and reinfection, we examined the likely impact of different strategies for morbidity prevention. Results suggest the need for early, repeated treatment through primary school years to optimally prevent the disabling sequelae of stunting and undernutrition. Dynamics of infection/reinfection during childhood and adolescence, combined with early treatment effects against reversible infection-associated morbidities, create a need for aggressive retreatment of preadolescents to achieve optimal suppression of morbidity where drug-based control is used. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.