Antimicrobial cycling is the deliberate, scheduled removal and substitution of specific antimicrobials or classes of antimicrobials within an institutional environment (either hospital-wide or confined to specific units) to avoid or reverse the development of antimicrobial resistance. True antimicrobial cycling requires a return to the antimicrobial(s) that were first used. Testing of the hypothesis that cycling will result in a lower prevalence of resistance is ongoing, mostly occurs within intensive care units, and largely involves cycling regimens targeted for treatment of suspected gram-negative bacterial infections. Unfortunately, there has been insufficient study to determine whether any meaningful impact on resistance has occurred as a result of a cycling program. Mathematical models question the usefulness of cycling as an infection-control method. Published studies demonstrate that cycling may be one way to change prescribing practices by clinicians without sacrificing patient safety. However, optimizing antimicrobial use through traditional and novel methods (e.g., computer decision support) should not be abandoned.