Since 1892, anatomical studies have demonstrated that the retinas of mammals, including humans, receive input from the brain via axons emerging from the optic nerve. There are only a small number of these retinopetal axons, but their branches in the inner retina are very extensive. More recently, the neurons in the brain stem that give rise to these axons have been localized, and their neurotransmitters have been identified. One set of retinopetal axons arises from perikarya in the posterior hypothalamus and uses histamine, and the other arises from perikarya in the dorsal raphe and uses serotonin. These serotonergic and histaminergic neurons are not specialized to supply the retina; rather, they are a subset of the neurons that project via collaterals to many other targets in the central nervous system, as well. They are components of the ascending arousal system, firing most rapidly when the animal is awake and active. The contributions of these retinopetal axons to vision may be predicted from the known effects of serotonin and histamine on retinal neurons. There is also evidence suggesting that retinopetal axons play a role in the etiology of retinal diseases.