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The recent emergence of strains of drug-resistant Streptococcus pneumoniae (DRSP) is a serious clinical and public health problem. Several interventions have been proposed to limit the further emergence and spread of DRSP, including campaigns for appropriate antibiotic use and the introduction of pneumococcal conjugate vaccines. Whether the current epidemic of drug resistance in S. pneumoniae is sustainable or will succumb to current efforts to limit its spread will be decided by an interaction of factors related to the pathogen (i.e., the relative fitness of the resistant strains), to the prescription of antibiotic treatment (i.e., changes in selection pressure), and to the host (i.e., the ability to slow the transmission of DRSP). Much investigation is still needed to better ascertain how maintenance of DRSP strains in the community at large is influenced by each factor and affected by current interventions that are based on these factors.