Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.