Model organisms are commonly used to study complex biology of receptors and their interactions. Zebrafish is a widely used tool to examine behavioral consequences of receptor ligand administration, receptor physiology, and to develop novel drugs. Similarities with mammalian brain structures and neurotransmitter systems, easy manipulation, and availability of mutant lines have facilitated this research. Histamine H1 receptor (hrh1) exists as a single copy in zebrafish genome. The properties of hrh1 are rather similar to the human receptor, except that the zebrafish hrh1 displays a 100-fold higher affinity for histamine than the human receptor. H2 receptor (hrh2) exists in two copies, of which hrh2a resembles the human receptor, whereas hrh2b does not bind histamine but displays constitutive activity. Three copies of H3-like histamine receptors exist in zebrafish genome. Fish lacking hrh3a show low levels of dopamine and serotonin and a normal sleep pattern. Adult hrh3a-lacking fish show increased anxiety-like behavior and reduced aggression in behavioral tests. No receptor characterized so far shares the properties of human or rodent H4 receptor.