Community-acquired respiratory tract infections (CARTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis, contribute substantially to health care costs in the United States. Although many prescriptions for antibiotics are written each year for the treatment of CARTIs, most are prescribed on an empiric basis. Concerns about the increasing prevalence of antimicrobial resistance and the changing pattern of pathogens isolated from subjects with CARTIs have raised questions about the empiric treatment paradigm. When choosing appropriate antimicrobial therapy for CARTIs, physicians must consider not only the spectrum of activity of antibiotics but also the potential risk of resistance. Telithromycin is the first member of the ketolide class, a new family of antimicrobials structurally related to the macrolides, to be approved by the US Food and Drug Administration for the treatment of CARTIs. The spectrum of activity of telithromycin includes common typical and atypical causative pathogens associated with community-acquired respiratory tract infections, including antibiotic-resistant strains of Streptococcus pneumoniae. Clinical trials have shown that telithromycin is as effective as traditionally used antimicrobial agents in the treatment of mild-to-moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis.