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Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a major cause of morbidity and mortality worldwide. Achieving long-term immunity against S. pneumoniae through immunization is an important public health priority. Long-term protection after immunization is thought to rely both on protective serum antibody levels and immunological memory in the form of antigen-specific memory B cells (MBCs). Although the ability to achieve protective antibody levels shortly after pneumococcal vaccination has been well documented for the various infant immunization schedules currently in use worldwide, the examination of immunological memory in the form of antigen-specific MBCs has been much more limited. Such responses are critical for long-term protection against pneumococcal colonization and disease. This review summarizes the published literature on the MBC response to primary or booster immunization with either pneumococcal polysaccharide vaccine (PPV23) or pneumococcal conjugate vaccines (PCVs), aiming to elucidate the immunological mechanisms that determine the magnitude and longevity of vaccine protection against pneumococcus. There is evidence that PCVs induce the production of antigen-specific MBCs, whereas immunization with PPV23 does not result in the formation of MBCs. Increased understanding of the immunological factors that facilitate the induction, maintenance and recall of MBCs in response to pneumococcal vaccination could enable the use of MBC enumeration as novel correlates of protection against S. pneumoniae. Ongoing studies that examine MBC response to pneumococcal vaccination in high burden settings will be extremely important in our understanding of long-term protection induced by pneumococcal conjugate vaccines. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.