Sir James Black developed beta-blockers, one of the most useful groups of drugs in use today. Not only are they being used for their original purpose to treat angina and cardiac arrhythmias, but they are also effective therapeutics for hypertension, cardiac failure, glaucoma, migraine and anxiety. Recent studies suggest that they might also prove useful in diseases as diverse as osteoporosis, cancer and malaria. They have also provided some of the most useful tools for pharmacological research that have underpinned the development of concepts such as receptor subtype selectivity, agonism and inverse agonism, and ligand-directed signalling bias. This article examines how beta-blockers have evolved and indicates how they might be used in the future.