Elevated heart rate in coronary artery disease (CAD) is known to induce myocardial ischemia, and its reduction is a recognized strategy to prevent ischemic episodes. In addition, elevated heart rate is an established risk factor for cardiovascular events in chronic heart failure (HF) and CAD. Accordingly, reducing heart rate improves prognosis in HF patients, as demonstrated in SHIfT (Systolic Heart Failure treatment with If inhibitor Ivabradine Trial). However, recent data from SIGNIfY (Study assessInG the morbidity– mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease) indicate this is not the case in CAD patients without clinical HF. Thus, heart rate is not a modifiable risk factor in this clinical setting, contrary to HF. Meanwhile, new clinical evidence has confirmed the benefits of heart rate reduction on angina symptoms, by improving microcirculation and coronary flow reserve, and stimulating arteriogenesis. Heart rate is also an important determinant of cardiac arrhythmias as heart rate reduction may be associated with atrial fibrillation and high heart rate after exercise to sudden death. Here, we critically review the new clinical findings and the role of heart rate along the cardiovascular continuum, and propose hypotheses for the differential effect of heart rate reduction in cardiovascular disease.