Streptococcus pneumoniae is a gram-positive human pathogen that is the leading cause of community acquired pneumonia and meningitis and a significant cause of otitis media, sinusitis, and bacteremia. Pneumococcal disease alone causes >1 million deaths worldwide each year. S. pneumoniae is surrounded by a polysaccharide capsule that protects the bacterium from uptake, or opsonophagocytosis, by host immune cells. S. pneumoniae produces 90+ capsular serotypes that vary in their sugar composition and complexity of the glycosidic linkages. Antibodies to the capsule have been shown to be protective against infection and the current commercial vaccines against S. pneumoniae contain the polysaccharide serotypes most commonly seen in invasive infection. Prevnar 7®, a heptavalent pneumococcal conjugate vaccine, manufactured by Wyeth (now part of Pfizer), was first licensed in the USA in 2000 and has become increasingly available worldwide. The vaccine protects infants as young as 2-months old. Over 100 million doses of Prevnar 7® have been distributed worldwide between 2000 and 2006, and it is the biggest blockbuster vaccine of all time with sales of $2.4 billion in 2007 and >$3 billion in 2009. Prevnar 13®, a 13-valent pneumococcal conjugate vaccine that confers increased protection with the addition of 6 more serotypes, was launched in early 2010, and is projected to eclipse >$5 billion in annual sales by 2014. Prevnar 13® has been approved for adults over 50 to address community acquired pneumonia infections and may generate an additional $2 billion in sales.