Sleep, an essential physiological process, has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS) in higher animals. REMS is a unique phenomenon that unlike other sleep-waking states is not under voluntary control. Directly or indirectly it influences or gets influenced by most of the physiological processes controlled by the brain. It has been proposed that REMS serves house-keeping function of the brain. Extensive research has shown that during REMS at least noradrenaline (NA)-ergic neurons must cease activity and upon REMS loss, there is increased level of NA in the brain, which then induces many of the REMS loss associated acute and chronic effects. The NA level is controlled by many bio-molecules, which are regulated at the molecular and transcriptional levels. Similarly, NA may also directly or indirectly modulate synthesis and levels of many molecules, which in turn may affect physiological processes. The burgeoning field of behavioral neuro-epigenetics has gained importance in recent years and explains the regulatory mechanisms underlying several behavioral phenomena. As REMS and its loss associated changes in NA modulates several pathophysiological processes, in this review we have attempted to explain on one hand how the epigenetic mechanisms regulating the gene expression of factors like tyrosine hydroxylase (TH), monoamine oxidase (MAO), noradrenaline transporter (NAT) control NA levels and on the other hand, how NA per se may affect other molecules in neural circuitry at epigenetic level resulting in behavioral changes in health and diseases. An understanding of these events will expose the molecular basis of REMS and its loss-associated pathophysiological changes; which are presented as testable hypothesis for confirmation.