The knowledge of the impact of beta-blockers on Coronary Flow Reserve (CFR) is based on experimental and clinical studies which used invasive methods (mainly Doppler Flow Wire, DFW) and non-invasive tools including scintigraphic (mainly Positron Emission Tomography, PET), magnetic resonance and Doppler ultrasound imaging. Beta-blockers have a large therapeutic indication in the treatment of coronary artery disease, due to their anti-ischemic and anti-arrhythmic effect. The anti-ischemic effect is based on the oxygen sparing mechanism with a reduction in rate-pressure product. Changes in coronary hemodynamics associated with the administration of beta-blockers have been extensively studied. These drugs may affect CFR by modifying either resting or maximal coronary blood flow (CBF) or even both. When assessing the impact of beta-blockers on CFR it is important to distinguish the effects exerted by first-and second generation beta-blockers from those due the mechanisms of third generation beta-blockers, which are provided of vasodilating action.