Beta-blockers are a heterogeneous group of antihypertensive agents. What they have in common is competitive antagonistic action on beta-adrenoreceptors (B1, B2 and B3). They differ in their receptor selectivity, intrinsic sympathomimetic activity (ISA), vasodilating properties and metabolism. Antihypertensive mechanisms and effect differ according to receptor-specificity and ISA, where differences in duration of action also have to be considered. An unfavourable metabolic profile of beta-blockers was reported based on studies describing the metabolic side effects of weakly-selective or non-selective agents. Newer generation beta-blockers appear to have a metabolic neutral profile. In systolic heart failure, three agents proved to improve survival up to 30%, mainly because of B1-blocking and/or vasodilating properties. The position of beta-blockers in treating diastolic heart failure remains uncertain. Beta-blocker therapy in coronary artery disease also leads to uncontested survival benefit, the cardioprotective mechanism largely due to rate reduction. This paper aims to describe the basis of heterogeneity of the available agents and to translate this into their applicability in different cardiovascular diseases, with focus on the underlying physiopathological mechanisms.