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Invasive meningococcal disease (IMD), although uncommon, is difficult to diagnose and can be rapidly fatal, even in healthy young persons. IMD is cyclic, and serogroups responsible for disease vary by age group, although the prevalence of the serogroups changes over time and by geographical location. Two quadrivalent vaccines are licensed in the United States to prevent IMD caused by serogroups A, C, Y, and W-135, and the US Centers for Disease Control and Prevention recommends routine vaccination with quadrivalent meningococcal conjugate vaccine of adolescents 11-18 years of age and vaccination of persons 2-55 years of age who are at elevated risk of IMD. Efforts to prevent IMD remain challenging, because there is neither an immunogenic vaccine for infants nor a vaccine to prevent serogroup B disease that is currently licensed. Obstacles to achieving optimal vaccine coverage among adolescents persist, and strategies are needed to address these shortcomings.