Age-related macular degeneration (AMD) is a progressive retinal disease, which is the leading cause of blindness in western countries. There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently. Until now, the pathogenesis of AMD has remained unclear, limiting the development of the novel therapy. Bruch’s membrane (BM) goes through remarkable changes in AMD, playing a significant role during the disease course. The main aim of this review is to present the crucial processes that occur at the level of BM, with special consideration of the lipid accumulation and protein modifications. Besides, some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium (RPE) cells transplantation were listed. Hopefully, this review may provide a reference for researchers engaged in pathogenesis or management on AMD.