Melatonin, a normal product of the pineal gland in animals and humans is mainly secreted at night. Available data suggest that in photoperiod mammals, melatonin is the pineal effector of gonadal involution. The impact of melatonin in human reproduction is still questionable. Melatonin has a more certain role in the regulation of human body rhythms, such as sleep and body temperature. Evidence in favor of a physiologic relationship between melatonin and the hypothalamic-pituitary-gonadal axis includes: women with hypothalamic ammenorrhea have elevated melatonin levels whereas in central precocious puberty levels are lower than normal. Melatonin treatment inhibited luteinizing hormone (LH) and 17 βestradiol (E2) secretion in normal women. Data have shown that melatonin is present in human semen. Supraphysiologic concentrations of melatonin had an inhibitory effect on sperm motility in vitro. Over the last decade we examined the possible relations between melatonin and the reproductive hormones in humans. Studies included: determination of serum, urine and seminal plasma melatonin concentrations in healthy human subjects and in patients with disorders of the reproductive system, evaluation of melatonin content in the human pineal gland and the demonstration of gonadotropin and gonadal steroid hormone receptors in the pineal gland. We also evaluated melatonin concentrations in hypogonadal and hyperandrogenic patients during androgen or antiandrogen treatment. Finally, we evaluated reproductive hormone concentrations and semen quality in healthy men during long-term melatonin therapy. The results of our studies are summarized in this review.