The basis of the RDS concept was the initial finding of Blum et al. [1] that the A1 (minor) allele of the D 2 dopamine receptor (DRD2) gene was associated with severe alcoholism, and later associations with smoking, obesity, and other substances and non-substance-disordered behaviors were identified [2,3]. This evidence concerns the gene DRD2 and obesity due to melanocortin 4 receptor deficiency.