Pneumococcus is a major cause of serious infections, especially among vulnerable populations. While pneumococcal conjugate vaccines (PCVs) provide effective protection against disease caused by the included serotypes, a substantial burden of disease remains. Several new PCVs are under development or were recently recommended for use to counteract the remaining disease burden. This had led to complicated policy deliberations on their optimal use in different populations. We discuss how key factors should be considered in any policy decision: serotype coverage of a new PCV, prevalence of the untargeted remaining serotypes, strength of the immune response to the serotypes in a new PCV, potential for PCV evasion, PCV costs, and optimal simultaneous use of PCVs in children and adults. We also suggest the need for robust analyses of available surveillance data and continual monitoring of changes in the pneumococcal serotypes that are responsible for disease and colonization to help decision makers make optimal recommendations.