Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and bacterial meningitis in adults. Despite the availability of potent antibiotics and the development of different pneumococcal vaccines, the burden of pneumococcal infections in terms of morbidity, hospitalizations, mortality, and healthcare costs continues to be tremendous. The different pneumococcal serotypes play an important role in some aspects of pneumococcal epidemiology. The introduction of the 7-valent conjugate vaccine among children led to important changes not only in the epidemiology but also in the clinical outcomes and mortality of invasive pneumococcal disease in adults. Moreover, with the widespread use of immunosuppressive and immunomodulating therapies for different medical conditions, we may expect an increase in the number of patients at a high risk of pneumococcal infections in the following years. The influence of immunosuppression as a risk factor for invasive pneumococcal disease, the changes in the dynamics of pneumococcal serotypes, the influence of pneumococcal serotypes on the clinical presentation of pneumococcal invasive disease, and the role of pneumococcal vaccines are some of the important issues that are discussed in this review.