In the following the impact of epicardial vessels on flow regulation in downstream resistive arteries and, vice versa, the potential influence of coronary microvascular disease on upstream conduit arteries will be reviewed. There is ample evidence that coronary artery disease of epicardial vessels leads to microvascular dysfunction not only due to a flow limiting stenoses with an altered regulation of vessel tone in the intra- and poststenotic segments, but also via distal microembolization of atherosclerotic material derived from upstream plaques. On the other hand, patients with hypertensive microvascular disease frequently reveal a disturbed endothelium-dependent and -independent regulation of epicardial vessel tone, although angiographic appearance is regular. Most strikingly, it could be demonstrated that in these patients with microvascular disease the incidence of coronary artery disease of epicardial vessels is increased several-fold as compared to age-matched populations. These findings suggest that hypertensive microvascular disease independent from the direct effect of hypertension on epicardial vessel affects upstream conduit arteries. Therefore a thorough and careful follow up of hypertensive patients with initially normal coronary arteriograms but preexistent microvascular disease appears advisable.