The majority of the currently used antiarrhythmic drugs carry serious proarrhythmic risk at the same time. Regarding class 3 agents, their torsadogenic action, which is associated with the reverse rate-dependent mode of action of these drugs, is the most serious side-effect. This mini-review provides a mass of evidence suggesting that the reverse rate-dependent nature of class 3 antiarrhythmic drug-effects is a common feature of all cardioactive agents in human cardiac tissues, consequently, development of selective blockers of the rapid delayed rectifier K⁺ current (I_Kr) without reverse rate-dependent properties has little chance to succeed. A more promising approach might be to combine prolongation of action potential duration with interventions suitable to minimize arrhythmogenesis at slow heart rates. This can likely be achieved by combining K⁺ channel blocking drugs with blockers of plateau inward currents, such as L-type Ca²⁺ current and window Na⁺ current. This view is supported by the results obtained by either combining two distinct molecules, or by applying single drugs having intrinsically combined modes of action.