Urinary tract infections are one of the most common reasons for antimicrobial prescriptions, however urine cultures are often unavailable and the choice of antibiotics is therefore empiric. The ideal antimicrobial agent must have specific pharmacokinetic and pharmacodynamic characteristics and an adequate spectrum of activity in order to obtain the potential eradication of the pathogen from the site of infection, minimizing the risk of recurrences and ensuring the best safety profile. There are several factors to be considered in the therapy choice: the type of infection, the increasing presence of extended-spectrum beta-lactamase (ESBL) producing bacteria showing resistance to most antibiotics and the problem of the bacterial internalization, that is a frequent cause of treatment failure and early recurrences. Prulifloxacin is a recent oral fluoroquinolone antibiotic approved in several European countries for the treatment of lower urinary tract infections and shows some interesting advantages in comparison with other antibiotics.