Invasive pneumococcal disease (IPD) is a major cause of pediatric morbidity and mortality in resource-rich and low and middle-income countries (LMICs). Streptococcus pneumoniae can cause a wide spectrum of invasive and non-invasive disease. In resource-rich countries, implementation of 7-valent pneumococcal conjugate vaccine (PCV7) has been a significant public health achievement. Dramatic decrease in pediatric IPD incidence occurred after PCV7 implementation, but emergence of multi-drug-resistant non-vaccine serotypes (especially 19A) remains a concern. The recently introduced 13-valent PCV (PCV13) has the potential to further reduce the burden of IPD due to serotypes not contained in PCV7. Given the diversity of pneumococcal serotypes and the possibility of serotype replacement disease, innovative approaches to development of pneumococcal vaccines are needed. Continued surveillance of pneumococcal serotypes and antimicrobial resistance is crucial to evaluate the impact of PCV13 vaccine. Improved access to PCVs is crucial to reduce morbidity and mortality related to IPD in LMIC.