Age-related macular degeneration (AMD) is the most important cause of blindness and visual impairment among the elderly. Nuclear receptors represent one of the largest families of transcription factors, with 48 present in the human genome. They are critical regulators and modulators of developmental and physiological processes and are both targets of drugs and chemicals of environmental significance. Many of the cellular processes regulated by nuclear receptors are disrupted in AMD. With this in mind, we recently created a nuclear receptor atlas of retinal pigment epithelial (RPE) cells, cells affected in AMD, highlighting the expression of all the nuclear receptors. The results of which provided scaffold to study individual receptors in aging and disease. This study led to several candidate receptors that have become the focus of detailed studies regarding their mechanistic role in the eye. One example of a nuclear receptor potentially relevant to AMD pathobiology is presented.