Both, pruritus and pain are aversive, but clearly distinct sensations originating in the peripheral and central nervous system. During the last years, many interactions between itch and pain in acute transmission and sensitization processes have been identified. It is common experience that the itch sensation can be reduced by the painful sensations caused by scratching. Vice versa analgesia may reduce this inhibition and thus enhance itch. This phenomenon is particularly relevant to spinally administered mu-opioid receptor agonists, which induce segmental analgesia often combined with segmental pruritus. The peripheral and central sensitization to pain and to itch exhibits striking similarities. Classical inflammatory mediators such as bradykinin have been shown to sensitize nociceptors for both itch and pain. Also regulation of gene expression induced by trophic factors, such as NGF, plays a major role in persistently increased neuronal sensitivity for itch and pain. Finally, itch and pain exhibit corresponding patterns of central sensitization. The knowledge of antagonistic interaction, but also of similar sensitization processes has major implication for antipruritic therapeutic approaches.