In this review we aim to provide the reader with an understanding of the capsular-based complexity of Streptococcus pneumoniae, one of the main limitations to current vaccine development. We then discuss the need for a new vaccine strategy based on proteic antigen candidates discovered in silico. Describing specifically how reverse vaccinology coupled to conventional vaccinology has led to a new paradigm of vaccine development. Finally, we conclude with the importance of defining the pan-genome of the pneumococcus, that is, the sequencing and analysis of multiple genomes from the same species. A critical factor in determining conserved proteins in a group of epidemiologically relevant circulating S. pneumoniae strains, in order to achieve the greatest coverage. Ultimately, the identification of immunogenic surface antigens and assessment of their efficacy will be imperative in the development of a vaccine with the ability to protect against invasive disease independent of serotype.