Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the ‘Polyvagal Theory’, certain limbic structures that serve as a ‘higher brain equivalent of the parasympathetic nervous system’ play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch.