Several epidemiological studies have reported that an elevated heart rate is associated with coronary atherosclerosis independently of other risk factors. In this review we explore the pathophysiologic mechanisms involved in the pro-atherosclerotic effect of elevated heart rate, apart from its association with sympathetic tone. An elevated heart rate enhances the magnitude and frequency of the tensile stress imposed on the arterial wall and prolongs the exposure of coronary endothelium to the systolic low and oscillatory shear stress. Moreover, increased heart rate intensifies the pulsatile motion of the heart and, therefore, the frequency of the periodically changing geometry of the coronary arteries, thereby affecting the local hemodynamic environment. All these processes induce structural and functional changes of the endothelial cells, which are accumulated over the time in atherosclerosis-prone regions promoting atherosclerosis. Heart rate should be considered in every patient with coronary heart disease, especially since it is an easily measurable and reproducible parameter. Slowing the heart rate could potentially decrease the progression of atherosclerosis by reducing the local pro-atherosclerotic vascular environment. This effect may be involved in any beneficial role of heart rate lowering agents in preventing coronary heart disease.