The ketolides represent a new subclass of antibiotics among the macrolide-lincosamide-streptogramin group. Telithromycin, the first ketolide to be awarded approvable status for clinical use, demonstrates in vitro activity against community-acquired respiratory pathogens including penicillin- and erythromycin-resistant Streptococcus pneumoniae. An extended half-life permits once-daily oral administration. Telithromycin is a substrate for cytochrome P450 (CYP) 3A4 and also inhibits drugs metabolized by CYP3A4. A relatively high frequency of mild-to-moderate gastrointestinal adverse effects has been reported. Similar clinical and microbiologic efficacy has been demonstrated with oral dosing in comparative clinical trials for community-acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, and pharyngitis. Although limited data on penicillin-resistant S. pneumoniae and erythromycin-resistant Streptococcus pyogenes are available from clinical trials, this drug appears promising for respiratory infections caused by these pathogens.