A 39-year-old male with a medical history significant for migraine, psoriatic arthritis, postural orthostatic tachycardia syndrome (POTS), vitamin D deficiency and hypoglycemia presented with a two-year history of sleep-related painful erections (SRPE). Since the reported prevalence is low, there is limited understanding of the possible etiologies of the disorder and little published clinical data on treatment algorithms. Thus, he had tried multiple therapies. Baclofen was effective but not tolerated. Pelvic physiotherapy and tadalafil were ineffective. Imipramine, clonazepam, vitamin B, iron, and selenium provided minimal benefit. Opiates were initially effective, but lost efficacy after 2-3 weeks. Finally, he was started on sodium oxybate after fully counseling the patient on the potential side effects of the treatment and consenting the patient for off-label use. This has effectively treated his SRPE. Sodium oxybate is a novel therapy for and a possible new treatment for this rare and challenging disorder that merits further study.