Histamine influences several immune/inflammatory and effector functions in addition to its dominant role in type I hypersensitivity reactions. Histamine can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization, and other functions leading to chronic inflammation. Histamine also regulates monocytes, dendritic cells, T cells and B cells, as well as related antibody isotype responses. The diverse effects of histamine on immune regulation appear to be due to differential expression and regulation of four types of histamine receptors and their distinct intracellular signals. In addition, differences in affinities of these receptors for histamine are highly decisive for the biological effects of histamine and drugs that target histamine receptors.