Clinicians have enthusiastically used fluoroquinolones owing to their good safety profile and wide range of indications. This article reviews fluoroquinolone pharmacology, pharmacodynamic principles, and fluoroquinolone resistance mechanisms, highlighting recent trends in the epidemiology of fluoroquinolone resistance among gram-negative organisms and Streptococcus pneumonia. Important fluoroquinolone safety concerns are discussed, along with indications for the most commonly used fluoroquinolones-ciprofloxacin, levofloxacin, and moxifloxacin.