Pneumococcus is a significant pathogen in neonates and in early infancy, particularly as a cause of invasive disease in sub-Saharan Africa where nasopharyngeal carriage rates are also exceptionally high. The pneumococcal-conjugate vaccines have now been rolled out in many high income settings and an increasing number of low and middle income countries. They have been highly effective at preventing vaccine serotype disease in infants. However, a window of susceptibility remains prior to the first vaccination at around six weeks of age. This paper summarizes the data available on both maternal and neonatal vaccination to prevent disease in newborns and early infancy and considers the key challenges and next steps for research in the field.