The hormone melatonin is released following a circardian rhythm with highest levels during the subjective night. It regulates a variety of physiological and neuroendocrine functions through activation of G-protein-coupled membrane receptors in target tissues. The lipophilic structure of melatonin also suggests an intracellular function and the nuclear receptor RZR/ROR was associated with a direct gene regulatory action of the hormone. In recent years, many putative ligands for membrane bound melatonin receptors have been synthesised, which represent indole derivatives or contain bioisosteric moieties and have structural elements identical or similar to the functional groups in the melatonin molecule. Two mammalian melatonin receptors (mt1 and MT2) with 60% homology at amino acid level have been cloned and simplify the search for selective agonists and antagonists. Recently, several ligands with a considerable selectivity for the MT2 receptor have been identified. In addition, many melatonergic compounds h...