Community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute sinusitis are among the most common bacterial infections encountered in clinical practice. Pathogens frequently associated with these infections include Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Unfortunately, resistance to antimicrobials commonly used for the treatment of these infections is increasing, limiting the clinical efficacy of these agents. Fluoroquinolones offer several advantages over other classes of antimicrobials used for the treatment of community-acquired respiratory tract infections. In general, fluoroquinolones have excellent in vitro activity against common respiratory pathogens, including some drug-resistant strains of S. pneumoniae. Microbial resistance to the newer fluoroquinolones is relatively uncommon, currently occurring in approximately 1% of clinical isolates in North America. Fluoroquinolones currently in clinical development may offer additional benefits over the marketed agents because they maintain good potency against isolates of S. pneumoniae displaying resistance to older quinolones (i.e., ofloxacin or ciprofloxacin) and may have a lower potential to engender resistance. This article reviews the in vitro activity of several newer fluoroquinolones, including agents currently in clinical development, against common respiratory pathogens, including antimicrobial-resistant strains. The mechanisms and prevalence of resistance of beta-lactam antimicrobials, macrolides, and fluoroquinolones also are reviewed.