The global emergence of pneumococci resistant to antimicrobial therapy has led to dilemmas in the management of pneumococcal infections. The principles of pharmacodynamics predict that penicillin and cephalosporin therapy of pneumonia will be successful against pneumococci with minimum inhibitory concentrations of penicillin up to 4 micrograms/ml. These predictions are supported by the observations of a number of recent clinical studies. Otitis media therapy is influenced by penicillin-resistance and current recommendations are that amoxicillin is the drug of choice for this infection, given at a double dose of 80 to 90 mg/kg/day. For the therapy of meningitis, cefotaxime or ceftriaxone in maximal doses is recommended and vancomycin may be added if cephalosporin-resistant strains are encountered with reasonable frequency in the population. The new fluoroquinolones with excellent antipneumococcal activity may be considered for use in the setting of pneumonia caused by highly resistant pneumococci and are under evaluation for the management of meningitis.