Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity. The most common bacterial cause of CAP is Streptococcus pneumoniae. The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents. Although microbiological breakpoints are useful for monitoring the emergence of resistance, the current National Committee for Clinical Laboratory Standards (NCCLS) guidelines make no distinction between clinical and microbiological breakpoints. Recent changes in NCCLS breakpoints for extended spectrum cephalosporins have provided a more meaningful approach to susceptibility testing and to consideration of the site of infection. Further controversy surrounds the clinical guidelines relating to CAP in terms of which antimicrobial agents should be given empirically to which types of patients. Within this review, the role of monotherapy versus the need for combination antimicrobial therapy, which often includes a macrolide and an extended spectrum cephalosporin such as ceftriaxone, is discussed. This review also discusses the various aspects of antimicrobial susceptibilities of S. pneumoniae, the drivers and influences of increasing resistance, the clinical relevance of this resistance and possible therapeutic options in the face of changing susceptibilities and mixed bacterial aetiologies. New guidelines from the IDSA attempt to embrace these changes.