Retinopathy is the most common complication of diabetes. The assessment of retinopathy signs presents clinicians a unique opportunity to directly visualize and assess the actual morphology of diabetic microvascular damage. Extensive studies have now shown that people with diabetic retinopathy have excess risks of systemic vascular complications, including subclinical and clinical stroke, coronary heart disease, heart failure, and nephropathy. There is also emerging evidence to suggest that diabetic retinopathy may share common genetic linkages with systemic vascular complications. The extant literature, therefore, supports the theory that diabetic retinopathy reflects widespread microcirculatory disease not only in the eye but also vital organs elsewhere in the body. Being a uniquely specific and non-invasively assessable measure of diabetic microvascular damage, retinopathy may also be envisioned as a novel biomarker of vascular disease risk in asymptomatic patients with diabetes. This review summarizes recent studies on the systemic associations of diabetic retinopathy, and discusses their pathophysiological significance and clinical implications.