The retinal vasculature can be viewed directly and noninvasively, offering an easily accessible window through which to study the human microcirculation in vivo and, therefore, early processes and pathways in cardiovascular disease (CVD) development. Recent advances in digital retinal photography and image analysis have allowed reliable and objective evaluation of retinal vascular pathologies (eg, retinopathy signs) as well as quantitative assessment of other topographic retinal vascular parameters, including retinal vascular caliber. An expanding series of clinical and epidemiologic studies now show that retinal vascular changes are associated with cardiovascular and metabolic diseases, including hypertension, diabetes, obesity, stroke, coronary heart disease, and heart failure. These data indicate that structural alterations in the retinal vasculature may mirror pathologic processes occurring in the systemic circulation and may represent novel biomarkers for CVD risk. This review summarizes the systemic cardiovascular associations of retinal vascular changes and discusses their clinical and research implications.