A number of fluoroquinolone agents are now available for clinical use and even more under development. Whether these compounds are equally effective and thus interchangeable in the treatment of urinary tract infection (UTI) has to be answered by comparing their antimicrobial activity against uropathogens, the pharmacokinetic and pharmacodynamic parameters and outcome of statistically meaningful clinical studies. Whereas almost all fluoroquinolones give equivalent results with short term therapy of acute uncomplicated cystitis in women, for patients with complicated UTI, only those compounds at the appropriate dosage regimen should be chosen for empiric therapy, which would exhibit sufficiently high urinary bactericidal activity against Gram-negative as well as Gram-positive uropathogens. When considering antibacterial activity, pharmacokinetic and pharmacodynamic properties as well as the results of the published clinical studies, a dosage of 500 mg ciprofloxacin twice daily, 500 mg levofloxacin once daily, or 400 mg gatifloxacin once daily may be comparable dosage regimens in the treatment of severe complicated UTI. In the case of ciprofloxacin (750 mg twice daily) and levofloxacin (500 mg twice daily), the dose could even be increased in UTI caused by less susceptible uropathogens, such as Pseudomonas aeruginosa.