The fluoroquinolone class of antimicrobials has been in clinical use for over 13 years. During that period, some representatives of the class have been extensively prescribed, such as ciprofloxacin and levofloxacin, while others have seen minimal use and have been restricted or withdrawn, namely, trovafloxacin and grepafloxacin. Manipulation of the fluoroquinolone structure by substituting a range of moieties around the core has yielded enhanced antibacterial activity, but in some cases this has come at a price. Specific substitutions are discussed in relation to particular recognized adverse events. In the present paper, newly introduced fluoroquinolones, such as moxifloxacin and gatifloxacin, are examined in terms of anticipated class effects and recent clinical experience. These antimicrobials are associated with reactions such as diarrhea, nausea, headache and other typical antimicrobial phenomena at rates less than 5%. New fluoroquinolone agents should be examined carefully in light of structural findings until adequate clinical data are amassed.