Itch is one of the alarm sensations that human beings have phylogenetically evolved for a defense purpose. Many theories and evidences regarding the biological, pathophysiological, and clinical aspects have been given, but an update on the neuroanatomy paths and consequent treatments is required. Some chemicals that are released after skin injury and facilitate the inflammatory process can induce itch or pain or basically lead to a sensitization of the nociceptor response. In clinical practice, the present authors note a continuum of sensations from touch to pain, among which many metaesthetic sensations can be described, even if the patients themselves cannot precisely define them. The specificity of itch neurons is therefore based on their spinal connections to the itch pathway rather than on unique peripheral receptors. The ambiguity of "itch unit" discharge to pruritics and algogens may be solved by the central inhibition of itch by pain: it is common knowledge that scratching relieves itching. Conversely, centrally acting pain-inhibiting opioids enhance itch by disinhibition. The relation between itch and pain is interesting in its clinical and physiopathological aspects in order to select appropriate treatment.