Histamine is one of the earliest identified mediators of allergy. Researchers identified its role in the modulation of allergic reactions as early as 1932. Since then, research has determined histamine to be a mediator of autoimmune conditions, gastric acid secretion, and hematopoiesis. Histamine is present within all bodily tissues; however, its sites of highest concentration include the lungs, basophils, and mast cells. It is also a potent vasoactive agent through its effects on bronchial smooth muscles and nociceptive itch nerves. Histamine regulates a variety of physiological functions by playing a key role in the inflammatory response of the body. It also has a vital role in various pathomechanisms of inflammatory diseases, which have led to the identification of novel histamine receptors over the years and greater recognition of its functions in the immune system.