Known since the 1950s, competitive β-adrenergic receptor antagonists, namely β-blockers (BB), constitute today a large and heterogeneous class of drugs with multiple clinical indications. Despite their daily use, can we choose the most appropriate BB for each of these indications? A better knowledge of the individual properties of BB (bioavailability, cardioselectivity, vasodilator and metabolic effects) could help to optimize their clinical benefits especially in polymorbid patients, frequently suffering from metabolic syndrome, peripheral arteriopathy or asthma/chronic obstructive pulmonary disease (COPD) supposed to be potential contraindications to their use.