Several clinical and epidemiological studies have concurrently illuminated established cardiovascular risk factors in age-related macular degeneration (AMD), raising the possibility that cardiovascular disease and AMD may share a similar pathogenic process. The vascular intima and the Bruch's membrane share several age-related changes and are the seat of many common molecules. Diseases of these structures may represent parallel responses to the tissue injury induced by multiple intercalated factors such as genetic variations, oxidative stress, inappropriately directed immune response or inflammatory disease complex. However, there are marked differences in the age-related changes in these two structures. The strategic location of the Bruch's membrane between the retinal pigment epithelium and the choriocapillaris can at least partially explain the differential susceptibility of AMD to cardiovascular risk factors. Unlike the vascular wall that is exposed to changes from the endothelium, the Bruch's membrane is subject to changes from both the endothelium (choriocapillaris) and epithelium (retinal pigment epithelium). Moreover, although both the vascular wall and Bruch's membrane become lipid laden with age, the lipid composition is characteristically different. This review examines the morphological and biochemical alterations in the senescent Bruch's membrane and its analogy to the vascular wall to evaluate the concurrence of atherosclerosis and AMD.