Penicillin-nonsusceptible Streptococcus pneumoniae isolates have become increasingly prevalent worldwide. They are well-known agents of community-acquired infections such as otitis media, pneumonia and bacterial meningitis. Therapy of pneumococcal infections is made difficult by the emergence and spread of bacterial resistance to penicillin and other beta-lactams, as well as other antimicrobials such as macrolides. This article reviews current concepts of epidemiology and the implications of penicillin-nonsusceptible pneumococci for management of community-acquired pneumonia and meningitis.