The only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed by the US Food and Drug Administration for use in patients younger than 18 years are complicated urinary tract infections, pyelonephritis, and postexposure treatment for inhalation anthrax. Nonetheless, approximately 520,000 prescriptions for fluoroquinolones were written in the United States for patients younger than 18 years in 2002; 13,800 were written for infants and children 2 to 6 years of age, and 2750 were written for infants younger than 2 years. Clinical trials of fluoroquinolones in pediatric patients with various diagnoses have been published and are reviewed. Fluoroquinolones cause arthrotoxicity in juvenile animals and have been associated with reversible musculoskeletal events in both children and adults. Other adverse events associated with fluoroquinolones include central nervous system disorders, photosensitivity, disorders of glucose homeostasis, prolongation of QT interval with rare cases of torsade de pointes (often lethal ventricular arrhythmia in patients with long QT syndrome), hepatic dysfunction, and rashes. The increased use of fluoroquinolones in adults has resulted in increased bacterial resistance to this class of antibacterial agents. This report provides specific guidelines for the systemic use of fluoroquinolones in children. Fluoroquinolone use should be restricted to situations in which there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria or to provide oral therapy when parenteral therapy is not feasible and no other effective oral agent is available.