Pneumococcal disease leads to considerable mortality, morbidity and healthcare cost worldwide, and disease rates are predicted to increase due to an aging population. There are over 90 different pneumococcal serotypes identified to date, each with unique capsular characteristics capable of eliciting serotype-specific immunity in its host. Several recent studies have demonstrated important differences in invasiveness, disease severity, complications from disease and antibiotic resistance patterns that are specific to individual serotypes. This knowledge is particularly pertinent given the ongoing seroepidemiological changes worldwide, partly due to the introduction of pneumococcal conjugate vaccination to childhood immunization schedules. Further characterization of pneumococcal serotype-specific clinical features, and continued surveillance of serotypes in nasopharyngeal carriage and disease, will help guide treatment and prevention strategies in pneumococcal disease.