Telithromycin is the first ketolide antibacterial to be approved for clinical use. The ketolides represent a novel class of antibacterial agents structurally related to the macrolides, which has been developed specifically to offer an optimal spectrum for the treatment of upper and lower respiratory tract infections (RTIs) caused by common and atypical pathogens, including strains that are resistant to currently used antibiotics. The innovative structural changes that distinguish telithromycin from macrolides contribute to its unique microbiological profile. Its well-balanced spectrum of antibacterial activity is highly appropriate for the empirical treatment of upper and lower community-acquired RTIs, offering activity against common, including resistant, and atypical/intracellular pathogens. Furthermore, telithromycin demonstrates a low propensity to select for or induce resistance to macrolide-lincosamide-streptogramin antibacterials. A once-daily dose of telithromycin 800 mg rapidly achieves high concentrations in both plasma and respiratory tissues and fluids and is maintained at effective levels throughout the 24-hour dosing period. In clinical trials, telithromycin has demonstrated high clinical and bacteriological efficacy in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis and group A beta-haemolytic streptococcal tonsillitis/pharyngitis. High efficacy was maintained in those patient groups considered to be at high risk of complications and those with infections caused by penicillin and/or macrolide (erythromycin) resistant Streptococcus pneumoniae. Together with its favourable tolerability profile and short course of once-daily therapy, these properties indicate that telithromycin will be a valuable new antibacterial for the empirical treatment of community-acquired RTIs.