Histamine is an endogenous biogenic amine that is ubiquitously distributed at various levels in different tissues. Histamine exerts its pleiotropic functions by activating four types of class A rhodopsin-like G protein–coupled receptors (GPCRs), named histamine H1, H2, H3, and H4 receptors, which are seven-transmembrane chain proteins that mediate the action of multiple molecules. Histamine acts at multiple levels, but its influence on ocular physiology and pathology is not fully understood. What is known about histamine is that it plays an important role in vision; in fact, each histamine receptor has been found in different parts of the eye. There are many experimental therapeutic strategies involving histamine receptors for the treatment of ocular diseases; actually, H1 receptor antagonists are used for the treatment of ocular allergies; moreover, in recent years, a beneficial effect of H3 receptor antagonists has also been shown for the treatment of ocular hypertension and neuroprotection. The results obtained in recent years are inconclusive, but a thorough study of the role of these receptors in vision could be an excellent therapeutic target for the treatment of ocular diseases with different pathogeneses.