Age-related macular degeneration (AMD) is the major reason of blindness of the elderly all over the world. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, the highly specialized region of the retina responsible for sharp and color visual acuity. Degeneration and cell death of retinal pigment epithelial cells (RPE) cause secondarily adverse effects on neural retina leading to visual loss. Most AMD patients cannot benefit from any treatment modalities. The prevalence of AMD is rising as a consequence of the aging of the population. As the RPE cells age, they are subject to continued oxidative stress and this believed to induce inflammation and progression of AMD. Interestingly, many clinical trials have revealed that dietary intakes of omega-3 fatty acids can reduce the risk of both early and late AMD, although their molecular targets in cellular signaling in AMD pathology are not understood. Recently, it has been proposed that the omega-3 fatty acid metabolites, resolvins and protectins, function as endogenous anti-inflammatory compounds. In this review, we propose that resolvins and protectins mediate their beneficial effects by preventing NF-kappaB signaling and this that may represent a new target for regulating the inflammatory responses in AMD.