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Three decades after the first nerve-sparing radical prostatectomy, postoperative erectile dysfunction (ED) remains a challenging and common problem. Despite considerable advances and improvements in surgical techniques, full recovery of erectile function remains elusive even for young, potent men. This suggests, ipso facto, that factors other than surgical technique must be important to recovery of erectile function.This study aims to review evidence that the prostate is an endocrine gland with contributions to local and systemic concentrations of 5α-dihydrotestosterone (5α-DHT), a potent androgen shown to be critical to penile physiology.Literature review of human and animal studies related to endocrine role of prostate and postoperative recovery of erectile function.Effect of 5α-DHT on erectile function and recovery after surgical injury.We advance the following hypothesis: “Loss of endocrine function of the prostate, specifically reduced local 5α-DHT concentration plays a major role in the failure of full recovery of erectile function following anatomic nerve-sparing radical prostatectomy.”We propose two separate, yet interrelated, mechanisms whereby the loss of 5α-DHT interferes with postoperative recovery of erectile function: (i) 5α-DHT contributes to cavernous nerve integrity and its ability to recover from surgical insult. (ii) 5α-DHT is important to the structural/functional integrity of penile tissues and erectile physiology. Kacker R, Morgentaler A, and Traish A. Medical hypothesis: Loss of the endocrine function of the prostate is important to the pathophysiology of postprostatectomy erectile dysfunction. J Sex Med 2014;11:1898–1902.