The increasing prevalence of beta-lactam and macrolide resistance in bacteria that cause respiratory infections has underscored the need for effective antimicrobial agents. The broad spectrum, excellent oral bioavailability, and once-daily dosing of fluoroquinolones contributed to the introduction of several new agents in the past decade. This class is among the world's most used antimicrobial therapies in community and hospital settings. Fluoroquinolones are generally well tolerated, but safety profiles differ widely among agents. Knowledge of in vitro activity, local microbiologic susceptibility and resistance patterns, adverse effects, and potential drug interactions should influence the selection of the best agent for individual patients. This overview of the fluoroquinolones directs particular attention to use in community-acquired pneumonia and safety.