Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and bacterial meningitis. Although effective antimicrobial drugs have reduced case fatality, the pneumococcus remains a leading global cause of morbidity and mortality. Therefore, prevention of infection by vaccination with the pneumococcal polysaccharide vaccine is recommended for persons at high risk for serious pneumococcal disease, such as the elderly and individuals with certain underlying medical conditions. Pneumococcal polysaccharide vaccines are safe and effective for the prevention of invasive infection among immunocompetent children and adults but are not immunogenic in infants. Conjugation of pneumococcal polysaccharides to a carrier protein improves immune responses among infants, and conjugate vaccines are currently being evaluated in large efficacy trials. The role of pneumococcal conjugate vaccines in adults has not been determined. Pneumococcal vaccines directed against pneumococcal proteins and DNA vaccines that induce anti-pneumococcal antibodies have been evaluated in animal models and may someday provide complementary or alternative methods for preventing pneumococcal infection. Improved utilization of the pneumococcal polysaccharide vaccine and continued development of improved vaccines are essential, and the emergence of drug-resistant strains of S. pneumoniae highlights the importance of preventing pneumococcal infections by vaccination.