In addition to its antioxidative effects melatonin acts through specific nuclear and plasma membrane receptors. To date, two G-protein coupled melatonin membrane receptors, MT(1) and MT(2), have been cloned in mammals, while the newly purified MT(3) protein belongs to the family of quinone reductases. Screening studies have shown that various tissues of rodents express MT(1) and/or MT(2) melatonin receptors. In humans, melatonin receptors were also detected in several organs, including brain and retina, cardiovascular system, liver and gallbladder, intestine, kidney, immune cells, adipocytes, prostate and breast epithelial cells, ovary/granulosa cells, myometrium, and skin. This review summarizes the data published so far about MT(1) and MT(2) receptors in human tissues and human cells. Established and putative functions of melatonin after receptor activation as well as the clinical relevance of these findings will be discussed.