Fluoroquinolones are highly effective antimicrobials for treating a variety of infections. There are four generations that differ in chemical structure. The pater generations are more effective than the earlier ones. Fluoroquinolones inhibit DNA replication by inhibiting bacterial DNA gyrase and topoisomerase IV. Resistance rapidly arises due to mutations in these enzymes. Other enzymes can protect the target enzymes from inhibition by fluoroquinolones. In addition, the SOS-response can lead to rapid development of resistance. A more detailed understanding of the mode of action and the processes causing the build-up of resistance is needed to prevent unnecessary resistance as a result of treatment with this class of antimicrobials.