Streptococcus pneumoniae is a major respiratory pathogen, causing 1·2 million deaths and 197 million pneumonia episodes globally in 2016. The spread of S pneumoniae to sterile sites, such as the blood and brain, leads to invasive pneumococcal disease. The best approach available for prevention of invasive pneumococcal disease in children and, more recently, adults is the use of pneumococcal conjugate vaccines (PCVs). PCVs are also highly effective at preventing colonisation and, thus, transmission, offering indirect protection to non-target immunisation groups such as adults—a characteristic that has been crucial in their success. However, PCVs only include and protect up to 20 of the 100 serotypes that can cause disease. The rise in adult cases of invasive pneumococcal disease from serotypes included in PCVs suggests indirect protection might be limited. Additionally, non-vaccine serotypes and some vaccine types that persist, some linked to antibiotic resistance, continue to cause disease. Future vaccine strategies include increasing the number of serotypes covered in PCVs for use in children and adults, broader vaccine use in adults, the development of adult-specific conjugate vaccines containing serotypes different from those covered in PCVs used in children, and protein vaccines, all of which will be explored in this Review. These strategies are expected to help mitigate the global burden of invasive pneumococcal disease in future years.