Purpose of review Pneumococcal infections are a major cause of morbidity and mortality worldwide. In recent years, Streptococcus pneumoniae has shown increasing resistance to a several antibiotics, becoming a worldwide problem. The impact of antibiotic resistance of S. pneumoniae on clinical outcomes is still controversial. The principal reason for this controversy is the existence of several factors related to the patients and to the pathogen that may influence how antibiotic resistance patterns affect clinical outcomes. The aim of this review is to discuss current knowledge of the epidemiological data on antibiotic resistance; we also discuss mechanisms and risk factors for antibiotic resistance. Recent findings The phenomenon of serotype replacement after the introduction of conjugate pneumococcal vaccinations and the escalation of antibiotic resistance worldwide remains an important issue in terms of their impact on clinical outcomes in pneumococcal disease. Antimicrobial resistance of pneumococcus leads to changes in the clinical presentation of pneumococcal disease, making it more difficult to diagnose and to treat. Consumption of antibiotics in the community is directly proportional to antimicrobial resistance. Carriage of S. pneumoniae and infection with antibiotic-resistant pneumococcus is associated with prior antibiotic therapy, extremes of age, presence of comorbidities (i.e. COPD), attendance at child day care centers, crowded conditions, intra-familial transmission, and nursing home residence. Summary Antibiotic-resistant S. pneumoniae is a worldwide problem. The implementation of several strategies including vaccine campaigns, prudent use of current antibiotics, and programs for the surveillance of pneumococcal infections, could limit the increasing resistance of this pathogen to antimicrobials.