The emergence of resistance to fluoroquinolones in virtually all species of bacteria was recognized soon after the introduction of these compounds for clinical use more than 10 years ago. Various resistance mechanisms, often interdependent, may explain different levels of resistance. Epidemiological factors, local antibiotic policies, patients' characteristics, origin of the strains, and geographic location are among the factors contributing to highly variable resistance rates. During the last several years, resistance to fluoroquinolones has remained very high among methicillin-resistant Staphylococcus aureus strains and in intensive care unit patients, and it has increased among nosocomial isolates of Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa. More worrisome are recent reports of an overall increase in resistance to fluoroquinolones among bacteria responsible for community-acquired infections, such as Escherichia coli, Salmonella species, Campylobacter species and Neisseria gonorrhoeae.