Antimicrobials of the fluoroquinolone class are involved in a number of clinically important drug‐drug interactions. Many of these interactions occur with all the available agents and exhibit little interpatient variability. In contrast, others occur only with specific fluoroquinolones and their extent varies markedly among subjects. The oral absorption of all fluoroquinolones is significantly impaired when coadministered with aluminum‐ and magnesium‐containing antacids and sucralfate, as well as with other metal cations such as calcium and iron. Concomitant use of these agents, even when dosed several hours apart, should be avoided. Enoxacin and ciprofloxacin impair the hepatic metabolism of theophylline and caffeine, leading to significantly increased serum concentrations. Ofloxacin and lomefloxacin have only minimal effects on xanthine metabolism. Case reports suggest that concomitant administration of several fluoroquinolones and warfarin, a drug that is also highly metabolized by the liver, leads to increased hypoprothrombinemic effects; prospective studies, however, failed to confirm this interaction. Clinicians must be aware of these and other potential drug‐drug interactions with fluoroquinolones for optimal use of the