The role of histamine as an important proinflammatory mediator has been well known for nearly 100 years. In regards to the immediate type allergic response, there is no debate about the importance of histamine. In addition, histamine has immunomodulatory functions, some of which are related to the histamine H2 receptor. However, with the discovery of the histamine H(4) receptor in the year 2000, the role of histamine as an immunomodulator became more obvious. The histamine H(4) receptor is expressed on several hematopoietic cells; along with the chemotaxis of immune cells, this recently characterized receptor modulates also the cytokine and chemokine secretion of some hematopoietic cells. Highly selective histamine H(4) receptor antagonists display promising results in animal models of allergic inflammatory diseases and also in in vitro studies on animal and human cells. These first results indicate that the histamine H(4) receptor is an interesting new pharmacological target for the treatment of allergic inflammatory disorders. This review summarizes the most important immunomodulatory functions of histamine and points to some possible indications in dermatology.