The use of retinal photography in clinical practice and research has substantially increased the knowledge about the epidemiology, natural history and significance of diabetic and hypertensive retinopathy. Early retinopathy signs, including retinal microaneurysms, blot hemorrhages, cotton-wool spots and hard exudates, are common vascular abnormalities found in middle-aged to older people with diabetes and hypertension. The presence of these early retinopathy signs is associated with an increased risk of systemic vascular diseases, such as stroke, cognitive impairment, coronary heart disease, heart failure and nephropathy. These retinopathy lesions may therefore be considered as biomarkers of systemic microvascular processes caused by diabetes and hypertension. Nevertheless, whereas the interest in retinopathy assessment continues to grow, a core concept remains undefined: what is the relative importance and contribution of diabetes and hypertension in the development of early retinopathy signs? The answer of this fundamental question holds the key to better understanding of the systemic associations of early hypertensive and diabetic retinopathy. In this review, we summarize the similarities and differences of early retinopathy signs seen in diabetes and hypertension, and discuss the conceptual relevance from epidemiological, pathophysiological, and clinical perspectives.