ciprofloxacin has no marketing authorization for use in neonates worldwide but it is prescribed for the treatment of neonatal life-threatening infections, mainly in developing countries and in Europe. Given the concerns about its toxicity in this population and the necessity for its use in specific clinical situations, we conducted a systematic review of the use of ciprofloxacin in neonates. we performed a systematic search of PubMed, Embase, and the Cochrane Database of Systematic Reviews and bibliographies of relevant articles. We included all studies, regardless of design, that reported efficacy, safety, and pharmacokinetics of ciprofloxacin for the treatment of any neonatal infectious condition. We excluded letters, editorials, preliminary reports, and abstracts. observational cohort studies, case reports, and descriptions of patient series account for all literature reviewed. Ciprofloxacin was administrated in neonates as a salvage therapy for sepsis due to multidrug-resistant strains or with signs of clinical deterioration under first-line antibiotic treatment. Initial administration was always intravenous with variable dosing schedule. Clinical response to treatment was estimated at 64% and 91% in 2 cohort studies, with a median of 83% in case series. Of the 14 case reports, 12 yielded positive clinical outcomes. No serious adverse events, particularly joint toxicity, were observed, although evaluation was predominantly clinical and follow-up limited to few months after the end of treatment. the current literature provides some information to support the use of ciprofloxacin in neonates. Additional high quality studies should be undertaken to provide reliable data on pharmacokinetics, efficacy, and long-term safety.