The action of most antiarrhythmic drugs which block cardiac ionic channels depends on heart rate, which is established as use- or frequency-dependence. This property is consistent with periodical drug (ligand) binding to channel binding sites which are transiently available during the excitation sequence of cardiac tissue. Antiarrhythmic drugs differ with respect to their binding and unbinding kinetics, i.e., with respect to their blocking and unblocking kinetics. This gives rise to different block-frequency relations and onset-kinetics of frequency-dependent ion channel blockade. Antiarrhythmic drugs have never been systematically compared with regard to their block-frequency relations. However, both the onset-kinetics as well as the block-frequency relation are essential in characterizing the frequency-dependent drug action, since both may be predictors of the anti- and pro-arrhythmic potential of antiarrhythmic drugs.