Streptococcus pneumoniae, commonly termed the pneumococcus, is a major pediatric pathogen both in developed and developing countries. Despite the availability of multiple antimicrobials to which this organism is susceptible, it continues to cause significant morbidity and mortality. Recognition of the limitations of antimicrobial therapy in controlling the consequences of infection, particularly among high-risk persons such as those who have underlying pulmonary or cardiovascular disease and the elderly, led to the introduction in the 1970s of a polyvalent, polysaccharide pneumococcal vaccine. As a result, the current indications for vaccination of both children and adults are based on risk factors for severe, potentially life-threatening pneumococcal infections and, in the case of children, the age-related immunogenicity of the polysaccharide antigens of this vaccine. Appropriate use of this vaccine is facilitated by knowledge of the pathogenicity of S pneumoniae, epidemiology of the infections it causes, and the immunogenicity and efficacy of the vaccine. The limitations of the current pneumococcal vaccine not only affect management of vaccinated patients but also have prompted development of investigational vaccines for use among infants and young children. Polysaccharide-protein conjugate pneumococcal vaccines that have increased immunogenicity in infants are in clinical trials and will be discussed only briefly in this review.