This article reviews the safety of fleroxacin in clinical trials. Data from 4,450 patients treated with oral fleroxacin and 650 treated with intravenous fleroxacin were analyzed. The overall rate of adverse reactions for patients treated with oral fleroxacin was 20% for those given 200 mg daily and 20% for those given a daily dose of 400 mg. The adverse reaction rate with the intravenous formulation was 20%. The most frequent adverse reactions involved the gastrointestinal tract (11%) and the central nervous system (9%). All events were reversible. Insomnia was the most commonly reported adverse event. The safety profile of fleroxacin was similar to that reported with other fluoroquinolones.