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Streptococcus pneumoniae (pneumococcus) remains an important cause of pneumonia, meningitis, bacteremias, and acute otitis media worldwide. Antimicrobial resistance among pneumococci has escalated dramatically over the past three decades, and is influenced by patterns of antibiotic use, population density, and spread of a few international clones.Globally, antimicrobial resistance among pneumococci spread rapidly in the 1990s, reflecting dissemination of a few clones. The incidence of resistance varies considerably among different geographic regions and is influenced by patterns of antibiotic use, population density, and local prevalence of resistant strains. The use of specific antibiotic classes not only predisposes to resistance to that class but also may facilitate emergence of resistance to unrelated antibiotic classes. Judicious usage of antibiotics may reduce the incidence of antibiotic-resistant pneumococci.Following usage of the pneumococcal conjugate vaccine in children, the incidence of invasive pneumococcal disease declined in both children and adults (reflecting herd immunity). However, emergence of serotypes not encompassed in the vaccine is worrisome, and may be associated with heightened antimicrobial resistance and virulence. Continued vigilance for emergence of novel serotypes and development of vaccines with expanded coverage and immunogenicity will be critical for optimal prevention of pneumococcal infections.