To review the chemistry, pharmacology, and safety of fluoroquinolones.A MEDLINE search (1966-July 2007) was conducted using the key words fluoroquinolones or quinolones with safety, adverse effects, hypoglycemia, hyperglycemia, dysglycemia, QTc prolongation, torsades, seizures, phototoxicity, tendon rupture, Clostridium difficile, and pseudomembranous colitis for articles published in the English language.Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the chemistry, pharmacology, and safety of each fluoroquinolone. Clinical trials were reviewed and included to compare the safety of systemic fluoroquinolones on the market. Literature on the pathology of serious adverse effects was also reviewed.Gatifloxacin has been shown to increase the risk of hospitalization for dysglycemia in patients with and without diabetes. Hyperglycemia may occur with any fluoroquinolone, especially if not properly dose adjusted. Hypoglycemia may occur with any fluoroquinolone and has a higher frequency in patients receiving concomitant oral hypoglycemic drugs or insulin. Use of any fluoroquinolone should be avoided in patients with risk factors for QTc interval prolongation or tendinopathy. All fluoroquinolones should be used with caution in patients with a history of seizure disorders and may cause phototoxicity or C. difficile-associated diarrhea (CDAD).Clinicians should be aware of possible alterations in blood glucose, QTc interval prolongation, seizures, phototoxicity, tendinopathy, or CDAD with the use of any fluoroquinolone, especially in patients with other risk factors for these conditions. Clinicians should closely monitor for these adverse effects and appropriately adjust doses to minimize these risks. To provide safe treatment for patients needing antibiotic therapy, an assessment of the risk-benefit ratio may be warranted in the decision to use a fluoroquinolone.