In addition, we discuss possible brain areas involved in orexin–serotonin cross‐talk; the role of serotonin receptors, transporters and uptake‐inhibitors in the pathogenesis and treatment of obesity; animal models of obesity with impaired serotonin‐function; single‐nucleotide polymorphisms in the serotonin system and obesity; and future directions in the orexin–serotonin field. Here, HCRT is linked to obesity due to melanocortin 4 receptor deficiency.