Background: Approximately 4 million cases of community-acquired pneumonia (CAP) occur in the United States each year, with the majority treated on an outpatient basis. The first fluoroquinolones (eg, ciprofloxacin) were used with caution for respiratory tract infections due to limited in vitro activity against common gram-positive pathogens. With the availability of levofloxacin, followed by gatifloxacin and moxifloxacin hydrochloride, which exhibited increased activity against gram-positive organisms, the fluoroquinolones have become a practical choice for the treatment of CAP. Objective: The aim of this review was to compare the respiratory fluoroquinolones in the outpatient management of CAP. Methods: We conducted a search for English-language articles (key terms: fluoroquinolone, levofloxacin, gatifloxacin, moxifloxacin, and pneumonia; years: 1996-2004). Data from published literature were reviewed regarding clinical and microbiologic efficacy and tolerability; pharmacokinetic and pharmacodynamic properties; and drug costs of levofloxacin, gatifloxacin, and moxifloxacin. Results: The 3 fluoroquinolones reviewed showed comparable clinical and microbiologic efficacy for the treatment of CAP. In general, the fluoroquinolones were well tolerated, although some differences have been reported, including higher rates of gastrointestinal and other adverse events for gatifloxacin and moxifloxacin. Gatifloxacin and moxifloxacin exhibited greater in vitro potency than levofloxacin against Streptococcus pneumoniae. However, levofloxacin achieved a higher serum drug concentration than the other agents, allowing similar attainment of pharmacokinetic and pharmacodynamic targets required for effective treatment. Conclusions: The respiratory fluoroquinolones provided appropriate first-line treatment in select patients with CAP on the basis of their microbiologic and clinical efficacy and their safety profiles.