The emergence of penicillin-resistant Streptococcus pneumoniae (PRSP) is an international problem which has been compounded by the development of high-level, multiple resistance to other beta-lactam antibiotics. Resistance develops in a 'step-wise' but unpredictable manner due to the mutation of penicillin-binding proteins (PBP). This results in a high degree of heterogeneity between bacterial strains. Such mutations can result in the rapid emergence of antibiotic resistance, including extended-spectrum cephalosporins, with reported minimum inhibitory concentration (MIC) values of up to 32 mg/l. The effective treatment of diseases caused by such organisms is dependent upon rapid assessment of antibiotic sensitivities. Therefore, MIC values of a range of antibiotics must be determined in cases of treatment failure and in serious pneumococcal infections. However, pharmacokinetic properties, as determined by the inhibitory quotient, which reflect drug concentrations attainable in different tissues, should also be considered. Beta-lactam antibiotics with good inhibitory activity against pneumococci include: amoxycillin, cefotaxime, ceftriaxone, cefpirome and imipenem. Nevertheless, as the prevalence of PRSP strains is likely to increase, new therapeutic strategies may have to be adopted.