Serious and invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide. The introduction of a hepatavalent pneumococcal conjugate vaccine (PCV7) in 2000 in the USA has had a significant impact on decreasing the incidence of serious and invasive pneumococcal disease in all age groups, especially in children under 2 years of age. However, the emergence of replacement nonvaccine pneumococcal serotypes (e.g., 19A, 3, 15 and 33) has resulted in an increase in the incidence of serious and invasive infections. The scope of disease caused by these emerging serotypes is not fully known, and the development of other pneumococcal conjugate vaccines is critical in order to control the amount of invasive disease that is currently being seen. The objective of this review is to discuss the current epidemiology of serious and invasive pneumococcal infections post-PCV7 introduction in the USA and review the pneumococcal vaccines that are in development.