Around 1-2% of teenagers above the age of 15 years and 2-6% of adults continue to wet the bed. Standard treatment often includes bladder advice, alarm therapy, desmopressin and anticholinergics. Tricyclic antidepressants (imipramine) can also be utilised. Unfortunately, most have limited efficacy and approximately half of children are refractory to treatment. The anti-enuretic effect of fluoxetine (a selective serotonin reuptake inhibitor – SSRI) was first reported by Mesaros in 1993. A number of studies have looked at the use of other SSRIs (sertraline, fluvoxamine and paroxetine) to treat night wetting. Here, Hussiny et al. have undertaken a single blinded, placebo-controlled trial between May 2020 and July 2021. Children had to be between eight and eighteen years of age and have severe (> seven wet nights per two weeks) refractory monosymptomatic nocturnal enuresis. Primary study outcomes were to assess the response rate according to the International Children’s Continence Society terminology (complete, partial and no response). A dose of 10mg fluoxetine was used daily. A total of 150 patients were enrolled. By the end of the study, 19 patients of the fluoxetine group and 21 of the placebo group were lost to follow-up. Fluoxetine resulted in a significantly lower number of wet nights per two weeks at four (4.7 vs. 9.7), eight (5.7 vs. 9.9) and twelve weeks (7.5 vs. 9.9) of treatment compared to placebo. After four weeks of fluoxetine, 7.1% of patients showed a complete response and 66.1% showed a partial response (compared to 0% and 16.7% respectively in the placebo group). However, the treatment response declined at 12 weeks and a complete response was seen in 10.7% and a partial response in 21.4% with fluoxetine (compared to 0% and 14.8% in the placebo group). Side-effects were noted in 9% and the medication discontinued. Although there was a high drop-out rate and follow-up was short (three months maximum), fluoxetine could be a potential addition to the urologist’s armoury for the treatment of a debilitating problem. Questions remain regarding optimal dosing – perhaps an increased dose might improve outcomes? Another consideration is that fluoxetine can be associated with increased suicidal thinking and suicidality in children, adolescents and young adults with major depressive disorders – it is a serious medication and should only be used when all other options have failed.