Streptococcus pneumoniae remains a major pathogen responsible for high morbidity and mortality in both the developed and developing world. During the last few years there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci, and the emergence of isolates with high-level resistance to extended-spectrum cephalosporins. In several countries, 50-80% of pneumococcal isolates, including the great majority of isolates of the serotypes associated with disease and carriage in children, are penicillin-resistant. Penicillin-resistant pneumococci are diverse, but in several countries successful highly penicillin-resistant clones (which in most cases are resistant also to tetracycline, chloramphenicol, and cotrimoxazole, and increasingly to erythromycin) have emerged, and some of these have spread globally. The effect of antibiotic resistance on the clinical outcome of otitis media, pneumonia and meningitis, and the potential of the new conjugate vaccines for controlling pneumococcal disease, are discussed.