Administration of opioids for analgesia may produce pruritus. It was believed, that this effect is mediated centrally by activation of μ-opioid receptors (MOR). However, recent data suggested that opioids may also mediate pruritus directly in the skin. A number of skin cell types, including keratinocytes, dermal mast cells, fibroblasts or macrophages, were shown to express both MOR as well as other opioid receptors. It was demonstrated, that the activation of MOR in the skin elicited pruritus, while activation of cutaneous κ-opioid receptors had anti-pruritic effect. Moreover, activation of opioid receptors in the skin modulated not only pruritus, but also inflammatory response. Taking these observations into consideration it could be suggested, that substances acting solely on peripheral opioid receptors could be potent anti-pruritic or even anti-inflammatory drugs, but devoided of typical side effects related to the activation of central opioid system.