Atopic eczema is one of the most pruritic skin diseases. Mediators of atopic eczema itch in the skin are still mostly unknown, but recent studies showed that the histamine 4 receptor plays an important role in itch pathophysiology; tryptase and interleukin-31 are also involved. Differences in itch perception and itch kinetics between healthy volunteers and eczema patients point towards an ongoing central nervous inhibitory activity in patients. Questionnaire studies reported comparatively higher loads in affective items chosen by patients with atopic eczema. In the concept of patient management, the therapy of clinical pruritus has to consider origin and perception of itch, namely the skin and the central nervous system, by combining topical and systemic treatment.