Fluoroquinolones have been studied for both uncomplicated and complicated skin and skin structure infections. Their broad spectrum, rapid bactericidal activity, extensive tissue penetration, excellent bioavailability and ease of administration have made these drugs a common choice for many infectious diseases, including skin infections. Extensive research has shown the fluoroquinolones to be as effective as beta-lactam antibiotics in managing a spectrum of diseases including erysipelas, cellulitis, impetigo, surgical wounds and diabetic foot infections. However, resistance to the fluoroquinolones has increased among the staphylococci, streptococci, Enterobacteriaceae and other important Gram-negative bacilli. Resistance has been linked directly to the widespread use of these compounds. Despite their appeal in the treatment of both uncomplicated and complicated skin infections, the fluoroquinolones should be reserved as alternatives to beta-lactams and other antibiotics or as empirical therapy in complicated infections until pathogens have been identified and drug regimens can be focused.