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Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide and has significant financial implications for health-care systems. The epidemiology and fundamental biology of the disease has evolved, reflecting the human immunodeficiency virus pandemic, increasing world travel, and, as always, poverty. The promise held out by molecular diagnostic technology has yet to deliver in this arena, and antibiotic resistance continues to drive the quest for new antimicrobial agents. The emergence of multidrug-resistant Streptococcus pneumoniae, the microorganism most often implicated as a cause of CAP, continues to threaten treatment options. The evolution of this organism, the persistently high mortality rate associated with CAP, and increasing health-care costs have prompted the publication of guidelines by various authorities that can be used to assist in the initial assessment of the patient and then guide empirical antimicrobial therapy. It is unclear whether these guidelines will have significant impact on cost and mortality, although the trend toward a rational and evidence-based approach to antimicrobial therapy must be a goal to aspire to.