Retinal microvascular signs, such as generalized retinal arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking and retinal haemorrhages, microaneurysms and cotton wool spots, are common fundus findings in the general population, even in individuals without hypertension or diabetes. Recent population-based studies have provided new insights into the systemic associations and clinical significance of these retinal signs. Studies show that these retinal microvascular signs are strongly associated with elevated blood pressure (BP). Generalized retinal arteriolar narrowing may be associated with markers of inflammation and risk of diabetes and hypertension. Retinal haemorrhages, microaneurysms and cotton wool spots are associated with risk of subclinical and clinical stroke, cognitive impairment, renal dysfunction and cardiovascular mortality, independent of BP and cardiovascular risk factors. A consistent pattern of association between retinal microvascular signs and ischaemic heart disease has not been demonstrated. This suggests that patients with some retinopathy signs (retinal haemorrhages, microaneurysms and cotton wool spots) may benefit from a careful systemic evaluation and, if supported by further research, appropriate risk reduction therapy.