All clinically used beta-blockers share the common feature of being competitive antagonists at beta-adrenoceptors. They differ, however, in additional pharmacological properties, such as beta1/beta2-selectivity ratios, presence or absence of intrinsic sympathomimetic activity (ISA), and/or local anesthetic activity. Furthermore, beta-blockers differ widely in their pharmacokinetic properties. The mammalian beta1- and beta2-adrenoceptors are the products of different genes but the receptor proteins show a certain degree of homology. Both span the cell membrane seven times. The cytoplasmic part of the receptor protein is the site of phosphorylations and hence involved in the process of receptor internalization. Upon exposure of tissues or organs to beta-blockers, characteristic changes emerge at the cellular level. There is an increase in the density of beta-adrenoceptors in the surface membrane, termed upregulation. This upregulation is subtype-specific, i.e., nonselective beta-blockers increase the density of both beta1- and beta2-adrenoceptors whereas beta1-selective antagonists upregulate only the former subtype. In contrast, beta-blockers with pronounced ISA downregulate beta-adrenoceptors. Beta-adrenoceptor density also changes in pathological situations. There is a downregulation of cardiac beta-adrenoceptors in dilated cardiomyopathy, probably as a consequence of increased sympathetic tone. A rapid upregulation of beta-adrenoceptors is characteristic of myocardial ischemia. This upregulation occurs in spite of a massive release of norepinephrine from cardiac adrenergic nerves during ischemia. Both norepinephrine release and upregulation of cardiac beta-adrenoceptors lead to an adrenergic overstimulation of ischemic myocardium. Blockade of beta-adrenoceptors inhibits the catecholamine component of this vicious circle and may explain part of the beneficial effects of beta-blockers in coronary artery disease and myocardial infarction.