Open AccessHistamine—the main product of mast cells plays critical role in the pathogenetic pathways of both allergic rhinitis and asthma. The novel concept of the unique airway diseases its only supported by the similarities within pathogenetic process. Antagonists of H1 and H2 receptors are quite effective in allergic rhinitis, but not effective enough in asthma. In an era of corticosteroids, leucotriene antagonists and Anti-IgE treatment, there is still a challenge to search for more effective, more acurate and more safe treatment option. Antagonists (inversive agonists) of histamine receptors H4 seems to be one of the promising targets in the allergic rhinitis and asthma treatment. The first H4 antagonist entered to clinics and the results from a proof-of-concept Phase II clinical study is expected to be disclosed soon. This review article summarizes current knowledge on H4R that have been collected in various studies sharing evidences about efficacy of H4R as a reasonable target for diseases with histamine involved pathogenetic pathways.