Lutein (L) and zeaxanthin (Z) are nutrients that reduce the risk of age-related macular degeneration (AMD). As micronutrients that selectively accumulate in the retina of the eye, L/Z can protect the macula from oxidative damage that contributes to AMD. This review will discuss the role of genes as a mediator between increased intake of dietary L/Z and decreased risk of AMD. Figure 1 outlines a pathway of L/Z that is subject to genetic influences, from 1) the diet to 2) the bloodstream to 3) the retina of the eye. First, L/Z are carotenoids that cannot be synthesized de novo and must be consumed from fruits and vegetables in the diet. Secondly, L/Z are transported by high-density lipoproteins (HDL) in the blood to the retina. Genetic variants that influence HDL status may impact the amount of L/Z that reaches retinal cells. Thirdly, L is taken up by retinal cells. Intracellularly, L down-regulates the expression of proinflammatory genes that contribute to the development of advanced AMD. Overall, L/Z are carotenoids in the diet that are transported by HDL and affect inflammatory pathways in AMD. The intersection of dietary L/Z, genes, and AMD will be reviewed using exemplary epidemiological, genome-wide association, and in vitro studies. The literature will support the integration of personalized nutrition, or dietary recommendations based on genomic information, into the field of eye care.