Healthcare decisions on vaccination programs mainly rely on the direct burden of illness and related costs of the disease. Next to the expected direct beneficial effect of pediatric immunization programs against Streptococcus pneumoniae, worldwide implementation of these programs has also been driven by the indirect beneficial impact as observed among various nontargeted age groups in Northern America. In this article, we provide a descriptive overview of the post-marketing surveillance and show that there are large differences in the observed disease epidemiology after implementation of pediatric pneumococcal immunization programs across countries. Possible factors responsible for these differences may include vaccine-serotype coverage, implemented vaccination schedules, antibiotic resistance rates and pneumococcal disease incidence prior to vaccination. A potential limitation can be found in the installation or enhancement of existing surveillance systems as well as other potential confounding bias, which may have influenced observed disease rates in the included observational studies. We conclude that the health and economic impact should be addressed in light of the country specific pneumoccocal disease epidemiology to support decisions on immunization programs.