Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including radioligands and give an update on the latest phenotyping results of melatonin receptor knockout mice. The current status and perspectives of the structure of melatonin receptor structures will be summarized. The physiological importance of melatonin receptor dimers and biologically important and type 2 diabetes-associated genetic variants of melatonin receptors will be discussed. The role of melatonin receptors in physiology and disease will be further exemplified by its functions in the immune system and the central nervous system. Finally, antioxidant and free radical scavenger properties of melatonin and its relation to melatonin receptors will be critically addressed.