β-Blockers are used for a wide range of diseases from hypertension to glaucoma. In some diseases/conditions all β-blockers are effective, while in others only certain subgroups are therapeutically beneficial. The best-documented example for only a subset of β-blockers showing clinical efficacy is in heart failure, where members of the class have ranged from completely ineffective, to drugs of choice for treating the disease. Similarly, β-blockers were tested in murine asthma models and two pilot clinical studies. A different subset was found to be effective for this clinical indication. These findings call into question the current system of classifying these drugs. To consider ‘β-blockers’, as a single class is misleading when considering their rigorous pharmacological definition and their appropriate clinical application.