Melatonin was initially extracted from the pineal gland and was thought to be produced exclusively by this organ. Subsequently it was shown that melatonin is also produced in other tissues including the gastrointestinal tract, retina and cells of the immune system. Melatonin is believed to be an important regulator of circadian and seasonal rhythms. Over the last thirty years, a great number of reports have documented a relationship between melatonin/pineal gland and the immune system in various species, including humans. In this review, current knowledge about the role of melatonin in the regulation of immune responses will be discussed.