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The pathology of atopic dermatitis is orchestrated on the cellular level by several different cell types in the characteristic skin lesions. In such lesions, histamine as a mediator of many biological functions is also present in high concentrations. Most of the cells involved in the inflammatory responses express the histamine H1 and H2 receptors, but drugs targeting these receptors are not clinically effective. The discovery of the fourth histamine receptor, which is differentially expressed on immune and nonimmune cells, has shed new light on the actions of histamine in the complexity of atopic dermatitis. In this review, we describe a possible genetic impact on the expression level of the histamine H4 receptor and summarize the current data regarding the activity of the histamine H4 receptor on the key effector cells in atopic dermatitis. We do so in the context of whether the histamine H4 receptor offers a novel target for effective treatments of inflammatory skin diseases.