Age-related macular degeneration (AMD) is an ocular disease and the main reason for sight loss in the elderly in the developed countries. The pathogenesis of the disease is complex and not fully understood, but involves several environmental and genetic risk factors. However, little is known about the role of epigenetics in this disease although it is recognized that epigenetic alterations often precede genetic changes in many pathological conditions and regulate aging and the developmental processes. There is experimental evidence for the involvement of DNA methylation and histone modifications in the pathogenesis of drusen formation, a central hallmark of AMD. However, the main impact of epigenetic modifications, including persistent lysine methylation of the H3 histone, is exerted during retinal embryonic development. This interplay opens an exciting possibility to manipulate the epigenetic pattern and to develop novel AMD therapies by physical, pharmacological or genetic interventions. One of the most intriguing questions is why different individuals develop different AMD phenotypes. Epigenetic regulation might open new perspectives into these changes in AMD pathology.