Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly throughout the world. AMD is attributed to a complex interaction of genetic and environmental factors. It is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium (RPE), and Bruch's membrane, as well as alterations in choroidal capillaries. Aging and age-associated degenerative diseases, such as AMD, are intimately associated with decreased levels of tissue oxygenation and hypoxia that may induce accumulation of detrimental RPE-associated deposits, inflammation and neovascularization processes in retina. Hypoxia-inducible factor (HIF) is the master regulator for hypoxia-induced cellular adaptation that is involved in NF-kappa B signaling and the autophagic protein clearance system. In this review, we discuss role of HIF in AMD pathology and as a possible therapeutic target. (C) 2009 Elsevier Ireland Ltd. All rights reserved.