Histamine is one of the most important biogenic amines in medicine and biology but its role in allergy, autoimmune and neoplastic diseases has not yet been fully defined. The last few years have brought many discoveries concerning important modulatory effects of histamine and its receptors on basic mechanisms of the immunological processes. The role of histamine H1 and H2 receptors in immunomodulation has been established. The immunomodulatory function of a newly described histamine H4 receptor has been revealed. One of the most important modulatory effects of histamine currently studied is its influence on T lymphocyte differentiation and function. Our present knowledge suggests that histamine may have a wider influence on various immunological processes than is now accepted; therefore, we need further studies to fully clarify the role of histamine and its receptors. This knowledge can bring new therapeutic solutions in allergies, autoimmune diseases and malignancies.