The beta-lactam antibiotics (penicillins and cephalosporins) are commonly prescribed for the treatment of community-acquired pneumonia. However, Streptococcus pneumoniae, the most common etiologic agent of community-acquired pneumonia, has become increasingly resistant to beta-lactams over the past decade. The results of several studies suggest that penicillins remain effective for streptococcal pneumonia when the infecting pathogen has a minimal inhibitory concentration (MIC) </=2 microgram/mL, presumably because the pharmacokinetic and pharmacodynamic parameters associated with current dosing regimens are still sufficient. However, when the MIC >/=4 microgram/mL, increased rates of mortality (for patients who survive their first 4 days of hospitalization) may occur. Currently, 3.5%-7.8% of S. pneumoniae clinical isolates have MICs that fall in this latter class, but these rates may rise in the future. The clinical relevance of in vitro resistance may be related to at least 3 factors: concordance of antimicrobial therapy, severity of illness, and virulence.