After 20 years of extensive practical experience in the management of glaucoma, beta-adrenergic blocking agents have gained a continuously increasing importance. The reason is a combination of effective reduction of intraocular pressure even during chronic treatment and few adverse effects. For many years, substantial effort has been focussed on the elucidation of the cellular mechanism inducing the intracellular pressure reduction. In this respect, mainly three different hypotheses have been controversially discussed: beta-blockers reduce aqueous humor formation (1) by an unspecific membrane-stabilizing process, (2) by impeding the local circulation of the ciliary body or (3) by specifically blocking adrenergic beta-receptors intimately involved in the regulation of aqueous humor production. Recently, substantial progress has been achieved by different working groups getting highly purified melanin-depleted fractions of ciliary epithelia which allow accurate receptor-ligand binding studies. The most important results, which all favor the explanation that the mechanism of action is due to specific inhibition of adrenergic receptors of the beta-2-subtype, are presented here. The consequences which result for the development of more specific pharmacologic agents in the future are discussed.