Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.