Streptococcus pneumoniae causes severe morbidity and mortality worldwide and poses a significant threat to the health and readiness of U.S. military personnel. Although a vaccine to prevent pneumococcal infections has been available for almost 25 years, its use has been limited. Recently, increasing antibiotic resistance among S. pneumoniae strains has emerged, prompting health care professionals to reevaluate the benefit of administering pneumococcal vaccine. The Naval Health Research Center, in collaboration with professionals from numerous civilian and military organizations, has initiated a rigorous double-blind, placebo-controlled trial investigating the operational value of vaccinating young adults as they enlist in the military.