Cardiovascular disease is one of the leading causes of death in industrialized nations worldwide. Traditional assessment of cardiovascular disease often involves invasive procedures (e.g., coronary angiography) and also provides little functional information of arterial reactivity. The emergence of the assessment of "subclinical" atherosclerosis and the role of arterial stiffness in both cardiovascular prognosis and cardiovascular risk have become more widely accepted and used in modern clinical practice and research. Flow-mediated dilatation can be used to directly assess endothelial function in healthy and diseased populations. This review aims to provide the reader with an insight into the technique and clinical applications of this recently new tool for the assessment of cardiovascular disease and risk.