This lecture examines the hypothesis that amplification of spatial dispersion of repolarization in the form of transmural dispersion of repolarization (TDR) underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies, including the long QT, short QT, and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia. In the long QT syndrome, amplification of TDR often is secondary to preferential prolongation of the action potential duration of M cells, whereas in Brugada syndrome, it is thought to be due to selective abbreviation of the action potential duration of right ventricular epicardium. In the short QT syndrome, preferential abbreviation of action potential duration of either endocardium or epicardium appears to be responsible for amplification of TDR. In catecholaminergic polymorphic ventricular tachycardia, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. Thus, the long QT, short QT, Brugada, and catecholaminergic ventricular tachycardia syndromes are pathologies with very different phenotypes and etiologies. However, these syndromes share a common final pathway in their predisposition to sudden cardiac death.