The histaminergic system in the brain is a phylogenetically old group of neurons that project to most of the central nervous system. It holds a key position in the regulation of basic body functions, including the sleep-waking cycle, energy and endocrine homeostasis, synaptic plasticity and learning. Four histamine receptors have now been cloned, and three of them are widely distributed in the mammalian brain. Here, we will discuss the localization, biochemistry and physiological functions of the components of the histaminergic system.