The role of β-adrenoceptor antagonists (β-blockers) in cardiovascular therapy has been subject to diverse trends and changes over the decades. With the advent of a wide variety of excellent drugs for the treatment of antihypertension, β-blockers have been relegated from the first-line treatment of essential hypertension. However, they remain the drugs of first choice in recommendations from the respective medical societies for heart failure, coronary artery disease, and atrial fibrillation as well as in hypertension complicated with heart failure, angina pectoris, or prior myocardial infarction. When indicated, cardioselective β-blockers should be prescribed in patients with diabetes mellitus or chronic obstructive pulmonary disease. We review the available evidence for the use of β-blockers in clinical conditions in which recommendations can be made for everyday practice.