Both exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) are associated with systemic vascular diseases and abnormalities. Although no uniform relationship between XFS/XFG and clinical systemic vascular diseases has been established across various populations, vascular dysfunction with or without clinically significant consequences has been repeatedly detected with both epidemiological and pathophysiological methods. Elevated plasma homocysteine, reduced cutaneous capillary flow reactions, damaged conduit artery dysfunction, impaired baroreflex sensitivity, parasympathetic cardiovascular neuropathy, and pathologic heart rate variability indices have all been shown in XFS and XFG. These pathophysiological alterations exceed the normal age-dependent decline and are considered strongly related to systemic elastosis and increased oxidative stress, but are not direct consequences of the presence of the risk alleles of the lysyl oxydase-like 1 gene. The mechanisms of the development of the clinically significant consequences (eg, increased frequency of myocardial dysfunction, stroke, aorta aneurism, and white matter lesions) are only partially understood. The current knowledge on vascular dysfunction in XFS/XFG is summarized in this article.