It is not unusual for practitioners to prescribe off-label drugs for their patients—that is, drugs that have not yet been approved by the Food and Drug Administration to treat the patient's particular condition. The decision to use off-label drugs should be based on a clear understanding of the risks and benefits to the patient. This issue is pertinent to WOC nurses because they may work with physicians who prescribe off-label drugs for their wound care patients. In addition, WOC nurses who are also nurse practitioners and have prescribing privileges may be intimately involved in the decision to prescribe off-label drugs. A review of the literature related to off-label drug use and mafenide acetate was conducted. This article presents the issues related to off-label use of mafenide acetate (Sulfamylon) and possible implications for patients with chronic infected wounds. (J WOCN 2001;28:253-8.)