OBJECTIVE: To review the complex role of the opioid system in reproduction and carbohydrate metabolism, abnormalities in the opioid system in women with polycystic ovary syndrome (PCOS), and the role of opioid antagonists in the management of PCOS-related infertility. DESIGN: Pertinent articles were identified through a computer PubMed search. References of selected articles were hand searched for additional citations. CONCLUSION(S): Endogenous opioids are generally considered inhibitory central neurotransmitters. Peripherally, opioids are involved in the regulation of pancreatic islet function, hepatic insulin clearance, and glucose metabolism, potentially contributing to the pathogenesis of hyperinsulinemia and insulin resistance in PCOS. The presence of sex steroids is required for normal function of the opioid system in both GnRH secretion and carbohydrate metabolism. In women with PCOS, growing evidence suggests dysregulation of the opioid system both centrally and peripherally, with complex interactions. The opioid system effects on carbohydrate metabolism appear to be modulated by obesity. Finally, naltrexone has been demonstrated to successfully augment traditional ovulation induction regimens, but has limited support as a single ovulation induction agent for PCOS.