Streptococcus pneumoniae (pneumococcus) remains a significant cause of both mild infections such as otitis media, sinusitis, and bronchitis and more severe manifestations such as bacteremia, pneumonia, and invasive pneumococcal disease. Several key serotypes have been targeted in vaccine development due to their association with increased infectivity. Pneumococcal vaccines are available in two formulations, the unconjugated purified polysaccharide (PPSV) and the conjugated formulation (PCV), which leads to a more robust and prolonged immune response. There have been dramatic reductions in mortality attributed to invasive pneumococcal disease over the past 2 decades due to improved vaccination rates and improved serotype coverage with the existing arsenal of vaccines (PCV13 and PPSV23). Utilizing both conjugate and purified polysaccharide modalities in series has produced greater and lasting immunity. The development of both the PCV15 and the PCV20 vaccines provides an opportunity to use conjugated vaccines against a wider spectrum of pneumococcal serotypes. National guidelines have been updated to incorporate the new pneumococcal vaccines into clinical practice.