The role of heart rate (HR) as an independent predictor of cardiovascular morbidity and mortality remains controversial. Direct evidence supporting a causal association between HR and prognosis is still lacking even if such relation appears plausible and may be inferred from epidemiological studies and clinical trials with HR lowering agents. The introduction of If current blocking agents, namely ivabradine, has offered the novel and unique opportunity to directly and exclusively interfere with HR and, thus, to validate the presence of a causal relationship between HR and prognosis. The BEAUTIFUL trial has recently confirmed that HR is a powerful negative prognostic predictor in patients with coronary artery disease and left ventricular systolic dysfunction. Particularly, subjects with a resting HR >70 b/min showed an increased risk of major adverse cardiovascular events. In these patients, HR reduction with ivabradine was associated with a reduction in major cardiac ischemic events, though not mortality. Further data will become available with the SHIFT trial in which patients with heart failure and HR > or =70 b/min are included and reduction in cardiovascular mortality and heart failure hospitalizations is the primary endpoint.