Genetic and environmental factors participate in the development of type 2 diabetes (T2D). Genome-wide association studies have revealed new genetic variants associated with T2D, including the rs10830963 variant located in the intron of the MTNR1B gene. This gene encodes the melatonin MT2 receptor, a member of the family of G protein-coupled receptors involved in the regulation of circadian and seasonal rhythms. This surprising result stimulated new investigations in the field of T2D to better understand the role of MT2 receptors and circadian rhythms in this emerging disease. The current article intends to cover this issue starting from the discovery of the first MTNR1B gene variants until the establishment of a functional link between MTNR1B variants and the risk of developing T2D and finishes by proposing some hypotheses that might potentially explain the importance of impaired MT2 function in T2D development.