On February 24, 2010, the US Food and Drug Administration approved a 13-valent pneumococcal protein conjugate vaccine (PCV13) for use in children. Currently, the only pneumococcal vaccine approved for use in adults in the United States is the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although PPV23 provides partial protection against invasive pneumococcal disease, it does not appear to impact the risk of pneumonia in elderly patients or younger adults with comorbidities. Experience with PCV7 in children and studies of the immunogenicity of PCV7 in high-risk adults suggest that PCV13 may be effective in adults. However, prior receipt of PPV23 may blunt the antibody response to protein conjugate vaccination; thus, receipt of PPV23 could potentially diminish the benefit of subsequent pneumococcal conjugate vaccination. The approval of PCV13 for children has created a unique dilemma for physicians seeking to provide optimum protection for their high-risk adult patients. Potential options could include use of the PCV13 “off-label,” perhaps followed by PPV23; withholding pneumococcal vaccination of adults while awaiting approval of PCV13; or continuing to use the PPV23. Although there are limited data on PCVs in adults, the availability of PCV13 for children will likely cause uncertainty for some physicians until there is updated official guidance regarding the optimum strategies for prevention of pneumococcal infection in adults.