Female stress urinary incontinence (SUI) is a common disease that involves leakage of urine during coughing, sneezing, or other increases in intraabdominal pressure. Treatments for SUI include pelvic floor muscle training, electrical stimulation, surgery, and off-label alpha-adrenergic agonists that stimulate contraction of the urethral smooth muscle. None of these treatments is universally or completely effective, and because drug therapy with the alpha- adrenergic agonists phenylpropanolamine and ephedrine can cause serious pressor adverse effects, the former has been banned in the United States, and the latter is under scrutiny. The central nervous system (CNS) affects reflexes that control urine storage and micturition, and norepinephrine and serotonin play a key role in maintaining storage capability by means of contraction of the external striated muscle of the urethral sphincter. Duloxetine hydrochloride, which inhibits reuptake of both of these neurotransmitters, has been shown to promote striated urethral sphincter contraction in animal models and to reduce the incidence of involuntary urine release in women with SUI without interfering with micturition. Neuromodulation of noradrenergic and serotonergic neurotransmitters with such drugs as duloxetine provides an additional treatment option for women with SUI.